lactoferrin and HIV-Infections

Host antimicrobial mechanisms reduce iron availability to pathogens. Iron proteins influencing the innate immune response include hepcidin, lactoferrin, siderocalin, haptoglobin, hemopexin, Nramp1, ferroportin and the transferrin receptor. Numerous global health threats are influenced by iron status and provide examples of our growing understanding of the connections between infection and iron metabolism.

Topics: Animals; Antimicrobial Cationic Peptides; Carrier Proteins; Cation Transport Proteins; Hepcidins; HIV; HIV Infections; Humans; Immunity, Innate; Iron; Lactoferrin; Lipocalin-2; Malaria; Mycobacterium tuberculosis; Plasmodium; Tuberculosis

HIV infection occurs primarily through mucosal surfaces, indicating that protection at mucosal sites may be crucial in prevention and treatment. The host innate and adaptive immune elements provide a level of protection, which differs between mucosal compartments, and appears to be most successful in the oral environment, where transmission is rare. In addition to the distinct oral mucosal architecture and cellular constituents, oral fluids, unlike other mucosal secretions, are rarely a vehicle for HIV infection. Multiple soluble factors may contribute to this antiviral activity, including neutralizing antibodies, secretory leukocyte protease inhibitor (SLPI), antiviral peptides such as defensins and cystatins, glycoproteins including thrombospondin and lactoferrin, and complement components. Understanding the antiviral activities of these and other potential resistance factors is becoming increasingly important in attempts to design treatments in the era of HAART resistance. In this regard, the mechanism of anti-HIV action of SLPI has recently been further elucidated by the discovery of its binding protein/receptor, which plays a key role in the infection of macrophages and may consequently be a novel therapeutic target. Continued elucidation of the unique features of mucosal HIV immunology is essential for understanding HIV pathogenesis and for developing effective vaccines and therapeutics.

Topics: Complement System Proteins; Cystatins; Defensins; Dendritic Cells; HIV Infections; Humans; Immunity, Mucosal; Lactoferrin; Macrophages; Mouth Mucosa; Proteinase Inhibitory Proteins, Secretory; Proteins; Saliva; Salivary Proteins and Peptides; Secretory Leukocyte Peptidase Inhibitor; Serine Proteinase Inhibitors; T-Lymphocytes; Thrombospondins

Human immunodeficiency virus (HIV) and many other viruses can be isolated in blood and body fluids, including saliva, and can be transmitted by genital-genital and especially anal-genital sexual activity. The risk of transmission of HIV via oral sexual practices is very low. Unlike other mucosal areas of the body, the oral cavity appears to be an extremely uncommon transmission route for HIV. We present a review of available evidence on the oral-genital transmission of HIV and analyse the factors that act to protect oral tissues from infection, thereby reducing the risk of HIV transmission by oral sex. Among these factors we highlight the levels of HIV RNA in saliva, presence of fewer CD4+ target cells, presence of IgA antibodies in saliva, presence of other infections in the oral cavity and the endogenous salivary antiviral factors lysozyme, defensins, thrombospondin and secretory leucocyte protease inhibitor (SLPI).

Topics: CD4-Positive T-Lymphocytes; Defensins; HIV Antibodies; HIV Infections; HIV-1; Humans; Immunoglobulin A, Secretory; Lactoferrin; Lactoperoxidase; Muramidase; Proteinase Inhibitory Proteins, Secretory; Proteins; RNA, Viral; Saliva; Salivary Proteins and Peptides; Secretory Leukocyte Peptidase Inhibitor; Sexual Behavior; Thrombospondins

Whey is a natural by-product of cheese making process. Bovine milk has about 3.5% protein, 80% of which are caseins and the remaining 20% are whey proteins. Whey proteins contain all the essential amino acids and have the highest protein quality rating among other proteins. Advances in processing technologies have led to the industrial production of different products with varying protein contents from liquid whey. These products have different biological activities and functional properties. Also recent advances in processing technologies have expanded the commercial use of whey proteins and their products. As a result, whey proteins are used as common ingredients in various products including infant formulas, specialized enteral and clinical protein supplements, sports nutrition products, products specific to weight management and mood control. This brief review intends to focus on scientific evidence and recent findings related to the therapeutic potential of whey proteins and peptides.

Topics: Anti-Bacterial Agents; HIV Infections; Humans; Immunity; Lactalbumin; Lactoferrin; Lactoglobulins; Milk Proteins; Oral Health; Oxidative Stress; Whey Proteins

There is a paradox that profound HIV-induced immunodeficiency is present systemically, whereas the majority of infections associated with HIV disease are present or initiated at mucosal surfaces. There is therefore a need to understand both specific and non-specific mechanisms of mucosal protection against HIV and its copathogens. The majority of HIV infections occur as a result of the passage of virus across mucosal membranes. Resistance to HIV infection at mucosal surfaces may be related to HIV-specific CD8+ T cell responses in some individuals and may be the basis for protective vaccine design. However, T-cells, macrophages and dendritic cells in mucosa may be a portal of entry for HIV. Transcytosis of HIV can occur from the mucosal to the submucosal surface and vice versa, and may be inhibited by mucosal immunoglobulins and neutralizing IgA within epithelial cells. HIV-induced alterations to oral epithelial cells, together with impairment of mucosal CD4+ T-cells and consequent altered cytokine secretion, may contribute to secondary infections. It also appears that HIV infection is associated with decreased salivary IgA levels, although a dichotomy between IgA concentrations in saliva and serum has been reported. Mucosal antibody responses, however, seem to be maintained. Considerable attention has been given to the possibility of mucosal immunization against HIV and there is evidence that secretory IgA antibody is neutralizing to different HIV strains. In addition to specific immune factors, it is likely that innate nonspecific factors may be significant in protecting mucosal surfaces, including lactoferrin, secretory leukocyte protease inhibitor, mucins, proline rich proteins and cystatins. These may be useful candidate virucides in topical preparations. Thus humoral, cellular and innate immune mechanisms, as well as lymphocyte-epithelial interactions, may all be impaired at mucosal surfaces as a result of HIV infection and may contribute to the susceptibility of mucosa to infective processes.

Topics: Antibodies, Viral; Antiviral Agents; CD8-Positive T-Lymphocytes; Cystatins; Cytokines; Dendritic Cells; Disease Susceptibility; Epithelial Cells; HIV; HIV Infections; Humans; Immunity, Mucosal; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulins; Lactoferrin; Macrophages; Membrane Proteins; Mouth Mucosa; Mucins; Peptides; Proline; Proline-Rich Protein Domains; Proteinase Inhibitory Proteins, Secretory; Proteins; Salivary Proteins and Peptides; T-Lymphocytes

A number of host and microbial factors have been shown to modulate HIV-1 infection. Their inhibitory effects are either HIV-specific or non-specific, and involve many different kinds of mechanisms. Among anti-HIV host factors are natural ligands or natural antibodies to HIV coreceptors, anti-inflammatory cytokines, interferons and several body fluid components (such as lactoferrin and prostaglandins). Microbial pathogens/factors that may suppress HIV-1 infection include lipopolysaccharide, scrub-typhus rickettsia, human herpesviruses-6 or -7, and GB virus C. While simple application of these HIV-suppressive factors for HIV-infected individuals is not realistic, investigation of mechanisms involved may lead to better understanding of HIV pathogenesis and help establish novel anti-HIV strategy.

Topics: Animals; Antibiosis; Cytokines; GB virus C; Herpesviridae; HIV Infections; HIV-1; Humans; Inflammation Mediators; Lactoferrin; Orientia tsutsugamushi; Receptors, Chemokine

Lactoferrin modulates mucosal immunity and targets mechanisms contributing to inflammation during human immunodeficiency virus disease. A randomized placebo-controlled crossover clinical trial of recombinant human (rh) lactoferrin was conducted among 54 human immunodeficiency virus-infected participants with viral suppression. Outcomes were tolerability, inflammatory, and immunologic measures, and the intestinal microbiome. The median age was 51 years, and the median CD4+ cell count was 651/µL. Adherence and adverse events did not differ between rh-lactoferrin and placebo. There was no significant effect on plasma interleukin-6 or D-dimer levels, nor on monocyte/T-cell activation, mucosal integrity, or intestinal microbiota diversity. Oral administration of rh-lactoferrin was safe but did not reduce inflammation and immune activation. Clinical Trials Registration: NCT01830595.

Topics: Antiretroviral Therapy, Highly Active; CD4-Positive T-Lymphocytes; Cross-Over Studies; Double-Blind Method; Female; Gastrointestinal Microbiome; HIV; HIV Infections; Humans; Immunity, Mucosal; Inflammation; Interleukin-6; Lactoferrin; Lymphocyte Activation; Male; Middle Aged; Recombinant Fusion Proteins; Viral Load

To explore the impact of race and geographic region on biomarkers of HIV risk and vaginal health, differences in soluble immune mediators were measured in US versus African and US white versus US black women at enrollment into a phase 2 microbicide trial.. Levels of soluble mucosal immune mediators and inhibitory activity against E. coli, which may serve as biomarkers of risk for HIV and other genital tract infections, were quantified in cervicovaginal lavage (CVL) collected from HIV-uninfected women in the United States (n = 73) and Africa (n = 73). Differences between groups were analyzed with multivariable logistic regression models for dichotomous variables and linear regression models for continuous variables.. Secretory leukocyte protease inhibitor, lactoferrin, human beta defensins, interleukin (IL)-8, and interferon-gamma-induced protein-10 were significantly higher in US compared to African women in multivariable analysis, but only IL-1β was significantly different between US white and black women. E. coli inhibitory activity did not differ among groups in adjusted analyses.. Differences in soluble mucosal immunity between US and African women may play an important role in women's risk for HIV and other genital tract infections and response to prevention strategies including vaginal microbicides and should be considered in future studies.

Topics: Adolescent; Adult; Africa; beta-Defensins; Biomarkers; Black or African American; Chemokine CXCL10; Cross-Over Studies; Cytokines; Escherichia coli; Female; Geography; HIV Infections; HIV-1; Humans; Immunity, Mucosal; Interleukin-1beta; Interleukin-8; Lactoferrin; Middle Aged; Mucous Membrane; Reproductive Tract Infections; Secretory Leukocyte Peptidase Inhibitor; United States; Vagina; Vaginal Douching; White People; Young Adult

This study examined the effect of an HIV vaccine on mucosal innate factor expression. Serum, gingival fluid, and genital mucosal secretions were collected from high-risk women and men enrolled in an HIV-1 efficacy vaccine trial and from low-risk women and men. Samples were tested by standard ELISA for lactoferrin, myeloid-related protein-8/14, and secretory leukocyte protease inhibitor. No consistent significant changes in innate factor levels were found in serum or secretions from vaccinees compared to placebo recipients or from high-risk compared to low-risk individuals. Because of the importance of innate immunity in host defense, evaluation of the mucosal innate immune system should be included in future HIV prevention trials.

Topics: Adolescent; Adult; AIDS Vaccines; Bodily Secretions; Calgranulin B; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; HIV Envelope Protein gp120; HIV Infections; HIV-1; Humans; Immunity, Innate; Immunity, Mucosal; Lactoferrin; Male; Middle Aged; Risk Factors; Secretory Leukocyte Peptidase Inhibitor; Vaccines, Synthetic

Periodontitis (PDT) has gained attention in the literature with the increase in life expectancy of people living with HIV on combined antiretroviral therapy (cART). Thus, the search for inflammatory biomarkers could be useful to understand the pathophysiology of chronic oral diseases in the cART era.. The aim of this study was to evaluate the impact of non-surgical periodontal therapy (NSPT) on clinical parameters of PDT, Candida spp. count and expression of lactoferrin (LF) and histatin (HST) in saliva and gingival crevicular fluid (GCF) of HIV-infected patients.. Bleeding index (BI), probing depth (PD), clinical attachment level (CAL), colonyforming units (CFUs) of Candida spp, and LF and HST levels were measured in saliva and GCF of both groups at three different times: baseline (before treatment), and 30 and 90 days after the NSPT. Clinical, mycological and immunoenzymatic analyses were also performed.. Twenty-two HIV-infected patients and 25 non-HIV-infected patients with PDT participated in the study. NSPT was effective in improving periodontal clinical parameters, including ≤ 4 sites with PD ≤ 5mm and BI ≤ 10%. Significant change in oral Candida spp. count occurred neither between the two groups nor after NSPT. And the salivary and GCF levels of LF and HST were not influenced by the NSPT; by contrast, except for salivary LF, HST and LF were shown to exhibit significantly higher levels in HIV-infected than in non-HIV-infected patients.. NSPT was effective in improving periodontal disease parameters in HIV-infected patients, but did not affect LF and HST expression in saliva and GCF of HIV-infected patients.

Topics: Candida; Gingival Crevicular Fluid; Histatins; HIV Infections; Humans; Lactoferrin; Periodontitis; Saliva

Topics: Animals; Curcumin; Female; HIV Infections; HIV-1; Lactoferrin; Nanoparticles; Rats; Tenofovir

Intriguing properties and structural dynamics of Lactoferrin have been exploited in numerous applications, including its use as self-assembling, pH sensitive nanoparticles to deliver intended cargo at the disease site. In this study, we explore the possibility of surface modification of Lactoferrin nanoparticles to hone its specificity to target HIV-1 infected cells. Existence of free cysteine groups on Lactoferrin nanoparticles available for reaction with external molecules facilitates conjugation on the surface with Sodium 2-mercaptoethanesulfonate (MES). Conjugation with MES is used to edge a negative charge that can mimic CCR5 and Heparan sulfate (initial point of contact of HIV-1 env to host cell surface) electrostatic charge (Sulfate group). A simple sono-chemical irradiation method was employed for self-assembly of Nanoparticles and for surface modification. The nanoparticles serve dual purpose to abrogate extracellular entry and to target viral enzymes, when loaded with ART drugs. The morphology and size distribution of the formed particles were explored using Transmission Electron Microscope (TEM), Scanning Electron Microscope (SEM) and Dynamic Light Scattering. Raman SERS was employed to understand the difference in the protein upon surface modification. The anti-HIV property of the particles was confirmed in-vitro. The modified device demonstrated acceptable nanoparticle properties with controlled release and higher effective concentration in the area of infection.

Topics: Anti-Infective Agents; Cells, Cultured; Drug Carriers; HIV Envelope Protein gp160; HIV Infections; HIV-1; Humans; Lactoferrin; Nanoparticles; Sulfonic Acids

Indinavir (IDV), an antiretroviral protease inhibitor used in treatment of HIV infection, has limited entry into brain due to efflux by the P-glycoprotein presented in blood-brain barrier. The aim of present study was to develop lactoferrin-treated nanoemulsion containing indinavir (Lf-IDV-NEs) for delivery to brain.. Indinavir-loaded nanoemulsions (IDV-NEs) were prepared by high-speed homogenization method, and then lactoferrin was coupled to IDV-NEs by water soluble EDC method.. The hydrodynamic diameters, polydispersity index, and zeta potential of IDV-NEs were 112 ± 3.5 nm, 0.20 ± 0.02, and -33.2 ± 2.6 mV, respectively. From in vivo studies in animal model of rats, the AUC. It can be concluded that applying both lactoferrin-treated and non-treated nanoemulsions clearly leads to significant brain penetration enhancement of indinavir, an effect which is more pronounced in the case of Lf-IDV-NEs with the higher drug residence time in brain.

Topics: Animals; Area Under Curve; Blood-Brain Barrier; Drug Carriers; Drug Liberation; Emulsions; HIV Infections; HIV Protease Inhibitors; Indinavir; Injections, Intravenous; Lactoferrin; Male; Nanoparticles; Permeability; Polysorbates; Rats; Rats, Sprague-Dawley

Lactoferrin is a member of the innate immune system acting in the first line of defence against pathogens, and it is known for its antibacterial, antifungal and antiviral activity, including HIV-1. Two polymorphisms, T29A and R47K, in the exon 1 region of the LTF gene (encoding for the lactoferrin protein) were previously described as able to influence the lactoferrin antimicrobial function.. LTF T29A and R47K genetic variants were analysed in a Zambian population to unravel if these polymorphisms could play a role in HIV-1 mother-to-child HIV-1 transmission.. LTF T29A and R47K polymorphisms were genotyped, using allelic specific fluorescent probes and real time PCR, in a population comprising 101 HIV-1 positive mothers and 333 children born to seropositive mothers.. Maternal LTF T29A A/A and A/G genotypes were found to be associated with decreased risk of HIV-1 MTCT, being more frequent among non-transmitter mothers respect to transmitter mothers.. Our data suggested that maternal LTF genetic background contributes to the susceptibility to HIV-1 transmission from mother to new-borns.

Topics: Adolescent; Adult; Alleles; Female; Genetic Predisposition to Disease; Genotype; HIV Infections; HIV-1; Humans; Infectious Disease Transmission, Vertical; Lactoferrin; Middle Aged; Mothers; Polymorphism, Single Nucleotide; Pregnancy; Public Health Surveillance; Risk Assessment; Risk Factors; Young Adult; Zambia

To enhance efficacy, bioavailability and reduce toxicity of first-line highly active anti-retroviral regimen, zidovudine + efavirenz + lamivudine loaded lactoferrin nanoparticles were prepared (FLART-NP) and characterized for physicochemical properties, bioactivity and pharmacokinetic profile.. Nanoparticles were prepared using sol-oil protocol and characterized using different sources such as FE-SEM, AFM, NanoSight, and FT-IR. In-vitro and in-vivo studies have been done to access the encapsulation-efficiency, cellular localization, release kinetics, safety analysis, biodistribution and pharmacokinetics.. FLART-NP with a mean diameter of 67 nm (FE-SEM) and an encapsulation efficiency of >58% for each drug were prepared. In-vitro studies suggest that FLART-NP deliver the maximum of its payload at pH5 with a minimum burst release throughout the study period with negligible toxicity to the erythrocytes plus improved in-vitro anti-HIV activity. FLART-NP has improved the in-vivo pharmacokinetics (PK) profiles over the free drugs; an average of >4fold increase in AUC and AUMC, 30% increase in the C

Topics: Alkynes; Animals; Anti-Retroviral Agents; Benzoxazines; Cell Line, Tumor; Cyclopropanes; Drug Combinations; Female; Half-Life; HIV Infections; HIV-1; Humans; Lactoferrin; Lamivudine; Male; Nanoparticles; Rats; Rats, Wistar; Tissue Distribution; Zidovudine

Mucosal immunity of the female genital tract plays a critical role in defense against sexually transmitted infections like HIV. Pregnancy is associated with both structural and immunologic alterations in the genital mucosa, but the impact of these changes on its ability to suppress HIV infection is unknown. Current epidemiologic data are conflicting as to whether pregnancy increases the risk of HIV acquisition.. The purpose of this study was to define the association between antimicrobial peptides and chemokines in cervicovaginal secretions and in vitro HIV infectivity among pregnant and nonpregnant women.. Forty pregnant and 37 nonpregnant women were enrolled in a prospective longitudinal cohort study at a single tertiary care women's hospital in Providence, RI. Cervicovaginal lavage was performed at each study visit. For pregnant women, study visits occurred once per trimester, and there was an optional postpartum visit. For nonpregnant women, study visits occurred across a single cycle that was timed to occur in the proliferative, ovulatory, and secretory phases based on the presumption of a regular menstrual cycle. The impact of cervicovaginal lavage on HIV infectivity was evaluated using a TZM-bl assay and compared between pregnant and nonpregnant women for each visit. The previously validated TZM-bl assay, which uses a luciferase reporting gene to indicate HIV infection of TZM-bl cells, was measured with a luminometer with higher relative light units that indicate greater levels of in vitro HIV infection. Immune mediators were measured with a multiplex bead assay. HIV infectivity and median concentration of each mediator were compared between pregnant and nonpregnant groups with the Wilcoxon rank sum test.. Cervicovaginal fluid from pregnant and nonpregnant women significantly decreased HIV infectivity in both groups compared with positive control (virus only; P<.01), but infectivity was not different between groups (P≥.44). During the second and third trimesters, pregnant women experienced suppression of several cervicovaginal immune mediators that included human beta defensin-2; lactoferrin; macrophage inflammatory protein-3α; regulated on activation, normally T-cell expressed and secreted; and stromal cell-derived factor-1 (all P≤.05). The antimicrobial peptide elafin was significantly correlated with HIV infectivity in both groups across all visits, except at the postpartum visit in the pregnant group (n=16). Secretory leukocyte protease inhibitor also was correlated significantly with infectivity across all visits, but in nonpregnant women only (P≤.03).. Cervicovaginal secretions from both pregnant and nonpregnant women contain immune mediators that are associated with HIV infectivity in an in vitro assay; however, infectivity was not different between pregnant and nonpregnant groups. If pregnant women are at increased risk for HIV infection, it is unlikely to be mediated by alterations in the effectiveness of these protective secretions.

Topics: Adult; beta-Defensins; Case-Control Studies; Cervix Uteri; Chemokine CCL20; Chemokine CXCL12; Elafin; Female; HIV Infections; HIV-1; Humans; Immunity, Mucosal; Lactoferrin; Longitudinal Studies; Pregnancy; Prospective Studies; Secretory Leukocyte Peptidase Inhibitor; Vagina; Vaginal Douching; Young Adult

This study compared lactoferrin (LF) levels in the gingival crevicular fluid (GCF) and saliva between HIV-infected and noninfected patients with chronic periodontitis.. For each subject, LF levels were analyzed in one shallow site (SS; PD ≤3 mm), one deep site (DS; PD >5 mm) and in resting whole saliva. Two groups, 28 HIV-infected and 10 noninfected, were selected.. Although the salivary LF levels were higher in HIV-infected than in noninfected individuals, especially in AIDS patients, this was not statistically significant (P > 0.05). Subgingival LF levels for SS and DS were lower among HIV-infected individuals, although AIDS patients showed the lowest levels. Age, smoking, gender, T CD4 lymphocytes levels and viral load did not influence subgingival LF levels, neither for SS nor for DP. Positive fungal culture was observed in 24 HIV-infected patients, but only observed in one in the control group. Overall, LF concentration was significantly higher in DS than SS, both in HIV-infected and noninfected individuals (P < 0.05) and salivary LF levels were always higher than GCF levels.. The data indicate that LF levels in the GCF and saliva are not different between HIV-infected and noninfected patients with chronic periodontitis.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Age Factors; Candida albicans; CD4 Lymphocyte Count; Chronic Periodontitis; Dental Plaque Index; Female; Gingival Crevicular Fluid; HIV Infections; Humans; Lactoferrin; Male; Middle Aged; Mouth Mucosa; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Saliva; Sex Factors; Smoking; Tongue; Viral Load; Young Adult

Bodily secretions, including breast milk and semen, contain factors that modulate HIV-1 infection. Since anal intercourse caries one of the highest risks for HIV-1 transmission, our aim was to determine whether colorectal mucus (CM) also contains factors interfering with HIV-1 infection and replication. CM from a number of individuals was collected and tested for the capacity to bind DC-SIGN and inhibit HIV-1 cis- or trans-infection of CD4+ T-lymphocytes. To this end, a DC-SIGN binding ELISA, a gp140 trimer competition ELISA and HIV-1 capture/ transfer assays were utilized. Subsequently we aimed to identify the DC-SIGN binding component through biochemical characterization and mass spectrometry analysis. CM was shown to bind DC-SIGN and competes with HIV-1 gp140 trimer for binding. Pre-incubation of Raji-DC-SIGN cells or immature dendritic cells (iDCs) with CM potently inhibits DC-SIGN mediated trans-infection of CD4+ T-lymphocytes with CCR5 and CXCR4 using HIV-1 strains, while no effect on direct infection is observed. Preliminary biochemical characterization demonstrates that the component seems to be large (>100kDa), heat and proteinase K resistant, binds in a α1-3 mannose independent manner and is highly variant between individuals. Immunoprecipitation using DC-SIGN-Fc coated agarose beads followed by mass spectrometry indicated lactoferrin (fragments) and its receptor (intelectin-1) as candidates. Using ELISA we showed that lactoferrin levels within CM correlate with DC-SIGN binding capacity. In conclusion, CM can bind the C-type lectin DC-SIGN and block HIV-1 trans-infection of both CCR5 and CXCR4 using HIV-1 strains. Furthermore, our data indicate that lactoferrin is a DC-SIGN binding component of CM. These results indicate that CM has the potential to interfere with pathogen transmission and modulate immune responses at the colorectal mucosa.

Topics: CD4-Positive T-Lymphocytes; Cell Adhesion Molecules; Cell Line, Tumor; Colon; Dendritic Cells; env Gene Products, Human Immunodeficiency Virus; HIV Infections; HIV-1; Humans; Lactoferrin; Lectins, C-Type; Mass Spectrometry; Mucus; Protein Binding; Protein Multimerization; Receptors, Cell Surface; Rectum

Saliva can be considered as an important actor during sexual intercourse. However, there is no data concerning its influence on HIV sexual transmission. The aim of this study was to evaluate the role of whole saliva on the in vitro secretion of CCL20 by monolayered HEC-1A endocervical epithelium cells. HEC-1A cells were cultivated in 96-well microplates and incubated with specimens of whole saliva collected from 57 subjects tested seropositive (n = 34) or seronegative (n = 23) for HIV and presenting different oral conditions (healthy periodontally, n = 22, and gingivitis/periodontitis, n = 35). The production of CCL20 in the supernatants of HEC-1A cells after overnight incubation at 37°C was quantified using ELISA. The salivary concentration of lactoferrin (Lf) and IL-1β was tested by ELISA. Saliva samples were found able to stimulate dramatically the production of CCL20 by epithelial cells, increasing this synthesis by a mean factor of 38.1 with reference to untreated cells. This stimulation was equivalent to that observed with IL-1β used as positive control. Although no difference was observed according to oral condition, HIV status or salivary concentration of Lf and IL-1β, the high salivary concentration of the latter protein could acknowledge in large part for the overproduction of CCL20 by HEC-1A cells when stimulated by saliva. Saliva was shown to significantly increase CCL20 secretion and may be responsible for an enhanced recruitment of dendritic/Langerhans cells at the genital level. These results suggest that saliva could facilitate HIV entry and possibly other pathogens through the genital mucosa during heterosexual intercourse.

Topics: Adult; Cell Line; Chemokine CCL20; Dendritic Cells; Disease Transmission, Infectious; Epithelial Cells; Female; HIV Infections; Humans; Interleukin-1beta; Lactoferrin; Male; Middle Aged; Saliva; Young Adult

We evaluated whether B cell-derived immune defenses of the gastro-intestinal tract are activated to produce HIV-specific antibodies in children continuously exposed to HIV via breast-feeding.. Couples of HIV-1-infected mothers (n = 14) and their breastfed non HIV-infected (n = 8) and HIV-infected (n = 6) babies, and healthy HIV-negative mothers and breastfed babies (n = 10) as controls, were prospectively included at the Complexe Pédiatrique of Bangui, Central African Republic. Immunoglobulins (IgA, IgG and IgM) and anti-gp160 antibodies from mother's milk and stools of breastfed children were quantified by ELISA. Immunoaffinity purified anti-gp160 antibodies were characterized functionally regarding their capacity to reduce attachment and/or infection of R5- and X4- tropic HIV-1 strains on human colorectal epithelial HT29 cells line or monocyte-derived-macrophages (MDM).. The levels of total IgA and IgG were increased in milk of HIV-infected mothers and stools of HIV-exposed children, indicating the activation of B cell-derived mucosal immunity. Breast milk samples as well as stool samples from HIV-negative and HIV-infected babies exposed to HIV by breast-feeding, contained high levels of HIV-specific antibodies, mainly IgG antibodies, less frequently IgA antibodies, and rarely IgM antibodies. Relative ratios of excretion by reference to lactoferrin calculated for HIV-specific IgA, IgG and IgM in stools of HIV-exposed children were largely superior to 1, indicating active production of HIV-specific antibodies by the intestinal mucosa. Antibodies to gp160 purified from pooled stools of HIV-exposed breastfed children inhibited the attachment of HIV-1NDK on HT29 cells by 63% and on MDM by 77%, and the attachment of HIV-1JRCSF on MDM by 40%; and the infection of MDM by HIV-1JRCSF by 93%.. The intestinal mucosa of children exposed to HIV by breast-feeding produces HIV-specific antibodies harbouring in vitro major functional properties against HIV. These observations lay the conceptual basis for the design of a prophylactic vaccine against HIV in exposed children.

Topics: Adaptive Immunity; Adult; B-Lymphocytes; Breast Feeding; Child; Feces; Female; HIV Antibodies; HIV Envelope Protein gp160; HIV Infections; HIV-1; Humans; Immunity, Humoral; Immunoglobulin Fab Fragments; Infant; Intestinal Mucosa; Lactoferrin; Milk, Human; Reference Standards; Species Specificity; Young Adult

The World Health Organization recommends human immunodeficiency virus (HIV)-positive mothers in resource-poor regions heat-treat expressed breastmilk during periods of increased maternal-to-child transmission risk. Flash-heat, a "low tech" pasteurization method, inactivates HIV, but effects on milk protein bioactivity are unknown. The objectives were to measure flash-heat's effect on antimicrobial properties of lactoferrin, lysozyme, and whole milk and on the digestive resistance of lactoferrin and lysozyme.. Flash-heated and unheated breastmilk aliquots from HIV-positive mothers in South Africa were "spiked" with Staphylococcus aureus and Escherichia coli and then cultured for 0, 3, and 6 hours. Lysozyme and lactoferrin activities were determined by lysis of Micrococcus luteus cells and inhibition of enteropathogenic E. coli, respectively, measured spectrophotometrically. Percentages of proteins surviving in vitro digestion, lactoferrin and lysozyme activity, and bacteriostatic activity of whole milk in heated versus unheated samples were compared.. There was no difference in rate of growth of E. coli or S. aureus in flash-heated versus unheated whole milk (p = 0.61 and p = 0.96, respectively). Mean (95% confidence interval) antibacterial activity of lactoferrin was diminished 11.1% (7.8%, 14.3%) and that of lysozyme by up to 56.6% (47.1%, 64.5%) by flash-heat. Digestion of lysozyme was unaffected (p = 0.12), but 25.4% less lactoferrin survived digestion (p < 0.0001).. In summary, flash-heat resulted in minimally decreased lactoferrin and moderately decreased lysozyme bioactivity, but bacteriostatic activity of whole milk against representative bacteria was unaffected. This suggests flash-heated breastmilk likely has a similar profile of resistance to bacterial contamination as that of unheated milk. Clinical significance of the decreased bioactivity should be tested in clinical trials.

Topics: Anti-Infective Agents; Breast Feeding; Developing Countries; HIV Infections; HIV-1; Hot Temperature; Humans; Infectious Disease Transmission, Vertical; Lactoferrin; Microbial Sensitivity Tests; Milk, Human; Muramidase; Risk Factors; Sterilization

Because of the risk of performing renal biopsies in children with co-morbid conditions, we carried out this study to identify candidate protein biomarkers in the urine of HIV-infected children with renal disease.. Urine samples from HIV-infected children with biopsy proven HIV-nephropathy (HIVAN; n = 4), HIV-associated Hemolytic Uremic Syndrome (HIV-HUS; n = 2), or no renal disease (n = 3) were analyzed by two-dimensional electrophoresis (2-DE) and proteomic methods. Positive findings were confirmed in HIV-infected children with (n = 20) and without (n = 10) proteinuria using commercially available assays.. By 2-DE analysis, a single urine marker was not sufficient to distinguish children with HIVAN from the others. High urine levels of beta(2)-microglobulin and retinol-binding protein (RBP) suggested the presence of tubular injury. In addition, we found elevated urine levels of iron and the iron-related proteins, transferrin, hemopexin, haptoglobin, lactoferrin, and neutrophil gelatinase-associated lipocalin (NGAL), in children with HIVAN and HIV-HUS. Furthermore, we detected a significant accumulation of iron in the urine and kidneys of HIV-transgenic (Tg) rats with renal disease.. These findings suggest that iron and iron-related proteins might be promising candidate urine biomarkers to identify HIV-infected children at risk of developing HIVAN and HIV-HUS. Moreover, based on the results of previous studies, we speculate that the release or accumulation of iron in the kidney of HIV-infected children may contribute to the rapid progression of their renal disease, and could become a new therapeutic target against HIVAN and HIV-HUS.

Topics: Acute-Phase Proteins; AIDS-Associated Nephropathy; Animals; Biomarkers; Biopsy; Blood Proteins; Case-Control Studies; Disease Models, Animal; Haptoglobins; Hemolytic-Uremic Syndrome; Hemopexin; HIV Infections; HIV-1; Humans; Iron; Lactoferrin; Lipocalin-2; Lipocalins; Predictive Value of Tests; Proteinuria; Proto-Oncogene Proteins; Rats; Rats, Transgenic; Time Factors; Transferrin

The polymorphism of the serine-rich Entamoeba histolytica protein (SREHP) among isolates obtained from different geographic regions was analyzed by a nested PCR followed by restriction analysis. Thirteen different profiles were generated from 23 E. histolytica isolates from Cameroon, Zimbabwe and South Africa while 20 others were generated from 38 E. histolytica PCR positive stool samples from South Africa. One of the profiles was common to isolates from Cameroon, Zimbabwe and South Africa and constituted the most prevalent (26.1%) of all the profiles. However, profiles unique to each country were also observed amongst the samples. A non-significant difference was observed between isolates from diarrheic and non-diarrheic samples. Of interest, of the five HIV positive stool samples three had the same profile indicating the possibility that some E. histolytica strains might be more common/pathogenic in immuno-compromised individuals. The results obtained showed that African isolates of E. histolytica may possess extremely complex genetic structures independent of geographic location. This study indicates that certain profiles might be responsible for the presentation of intestinal amoebic symptoms. However, more extended studies need to be performed in order to confirm these observations.

Topics: Adolescent; Adult; Aged; Animals; Cameroon; Child; Child, Preschool; Deoxyribonucleases, Type II Site-Specific; DNA, Protozoan; Entamoeba histolytica; Entamoebiasis; Feces; Female; Genetic Variation; HIV Infections; Humans; Infant; Lactoferrin; Male; Membrane Proteins; Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Protozoan Proteins; South Africa; Zimbabwe

Oral lactoferrin supplementation in human immunodeficiency virus (HIV)-infected, antiretroviral therapy-naïve children resulted in a skewing of T-lymphocytes towards more differentiated subpopulations. Phagocytosis (P=0.01) and killing (P=0.009), Toll-like receptor 2 expression (P=0.01) and the interleukin-12/interleukin-10 ratio (P=0.001) were also improved by lactoferrin. Lactoferrin supplementation results in immune modulation and could be useful in HIV infection.

Topics: Administration, Oral; Adolescent; Animals; Anti-HIV Agents; Cattle; Child; Child, Preschool; HIV Infections; Humans; Immunity, Innate; Lactoferrin; T-Lymphocyte Subsets

Innate immune factors in mucosal secretions may influence human immunodeficiency virus type 1 (HIV-1) transmission. This study examined the levels of three such factors, genital tract lactoferrin [Lf], secretory leukocyte protease inhibitor [SLPI], and RANTES, in women at risk for acquiring HIV infection, as well as cofactors that may be associated with their presence. Women at high risk for HIV infection meeting established criteria (n = 62) and low-risk controls (n = 33) underwent cervicovaginal lavage (CVL), and the CVL fluid samples were assayed for Lf and SLPI. Subsets of 26 and 10 samples, respectively, were assayed for RANTES. Coexisting sexually transmitted infections and vaginoses were also assessed, and detailed behavioral information was collected. Lf levels were higher in high-risk (mean, 204 ng/ml) versus low-risk (mean, 160 ng/ml, P = 0.007) women, but SLPI levels did not differ, and RANTES levels were higher in only the highest-risk subset. Lf was positively associated only with the presence of leukocytes in the CVL fluid (P < 0.0001). SLPI levels were lower in women with bacterial vaginosis [BV] than in those without BV (P = 0.04). Treatment of BV reduced RANTES levels (P = 0.05). The influence, if any, of these three cofactors on HIV transmission in women cannot be determined from this study. The higher Lf concentrations observed in high-risk women were strongly associated with the presence of leukocytes, suggesting a leukocyte source and consistent with greater genital tract inflammation in the high-risk group. Reduced SLPI levels during BV infection are consistent with an increased risk of HIV infection, which has been associated with BV. However, the increased RANTES levels in a higher-risk subset of high-risk women were reduced after BV treatment.

Topics: Adolescent; Adult; Cervix Uteri; Chemokine CCL5; Cohort Studies; Female; Heterosexuality; HIV Infections; HIV Seronegativity; HIV-1; Humans; Immunity, Innate; Lactoferrin; Risk-Taking; Secretory Leukocyte Peptidase Inhibitor; Unsafe Sex; Vaginal Douching; Vaginosis, Bacterial

In the present study, the prevalence and species distribution of Cryptosporidium among school children and hospital patients in the Venda region of South Africa was determined. Real time PCR (qPCR) was used for initial screening to detect positive samples while a nested PCR followed by restriction fragment length polymorphism was used to determine the species genotype. From a total of 244 stool samples tested, 44 (18%) had Cryptosporidium with no significant difference (chi(2)=0.04; P=0.841) between samples collected from patients attending hospitals 36/197 (18%) and the samples from primary schools 8/47 (17%). The age groups most affected were those from 2 to 5 years old (28.6%) and 50 to 59 years old (50.0%). Cryptosporidium was detected in 4 (12.5%) of the 31 HIV positive individuals. Fifty-seven percent of the Cryptosporidium positive samples were diarrheic and 26 (59.1%) had elevated lactoferrin content. C. hominis (82%) was more common than C. parvum (18%). This study has demonstrated the high prevalence of Cryptosporidium infections in the Venda region and its implications in causing diarrhea and inflammation.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Animals; Child; Child, Preschool; Cryptosporidiosis; Cryptosporidium; Feces; Female; Genotype; HIV Infections; Hospitalization; Humans; Infant; Lactoferrin; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Schools; Sex Distribution; South Africa

Several human mucosal fluids are known to possess an innate ability to inhibit human immunodeficiency virus type 1 (HIV-1) infection and replication in vitro. This study compared the HIV-1 inhibitory activities of several mucosal fluids, whole, submandibular/sublingual (sm/sl), and parotid saliva, breast milk, colostrum, seminal plasma, and cervicovaginal secretions, from HIV-1-seronegative donors by using a 3-day microtiter infection assay. A wide range of HIV-1 inhibitory activity was exhibited in all mucosal fluids tested, with some donors exhibiting high levels of activity while others showed significantly lower levels. Colostrum, whole milk, and whole saliva possessed the highest levels of anti-HIV-1 activity, seminal fluid, cervicovaginal secretions, and sm/sl exhibited moderate levels, and parotid saliva consistently demonstrated the lowest levels of HIV-1 inhibition. Fast protein liquid chromatography gel filtration studies revealed the presence of at least three distinct peaks of inhibitory activity against HIV-1 in saliva and breast milk. Incubation of unfractionated and fractionated whole saliva with antibodies raised against human lactoferrin (hLf), secretory leukocyte protease inhibitor (SLPI), and, to a lesser extent, MG2 (high-molecular-weight mucinous glycoprotein) reduced the HIV-1 inhibitory activity significantly. The results suggest that hLf and SLPI are two key components responsible for HIV-1 inhibitory activity in different mucosal secretions. The variation in HIV inhibitory activity between the fluids and between individuals suggests that there may be major differences in susceptibility to HIV infection depending both on the individual and on the mucosal fluid involved.

Topics: Anti-HIV Agents; Antibodies, Blocking; Cytotoxicity, Immunologic; HIV Infections; HIV-1; Humans; Immunity, Mucosal; Lactoferrin; Saliva; Secretory Leukocyte Peptidase Inhibitor

The aim of this study was the evaluation of connection between parodontium determined by using GI and PBI indexes and specific immunity status and non-specific in HIV infected group and in control group.. The study was carried out in the group of 37 patients infected with HIV. Mixed non-stimulated saliva was used for the study. Peroxidase activity was determined using the method by Mansson-Rahemtull. Lysozyme and A, G, M antibodies concentrations were determined with the use of radial immunodiffusion method. The concentration of lactoferrin was determined by using ELISA method. The clinical state of parodontium estimated by means of GI and PBI evaluating quality changes in the gum.. Deterioration of the immunological status of subjects was accompanied by the increase of the values of GI and PBI. The strong negative correlation between GI and PBI and the concentration of lactoferrin and positive activity of the peroxidase in the whole examined population was determined. In the infected group the correlation between the status of gingiva expressed by GI and concentration or activity of examined enzymes and immunoglobulins was not ascertained.. 1. HIV infection is connected to worsening of paradontium status expressed by values of GI and PBI indexes. 2. Paradontium status correlated positively with immunological status of HIV positive subjects. 3. In HIV infected group, no connection between number of IgA, IgG, IgM, concentration of lysozyme, lactoferrin, activity of peroxidase and paradontium status was observed.

Topics: Adult; Aged; Female; HIV Infections; Humans; Immunoglobulins; Lactoferrin; Male; Middle Aged; Muramidase; Periodontal Diseases; Periodontium; Peroxidase; Saliva

One of the cell types first encountered by human immunodeficiency virus type 1 (HIV-1) following sexual transmission are dendritic cells (DC). DC capture HIV-1 through C-type lectin receptors, of which the best studied example is DC-SIGN, which mediates HIV-1 internalization. DC can keep the virus infectious for several days and are able to transmit HIV-1 to CD4(+) T cells. We tested proteins from milk and serum for their ability to block DC-mediated HIV-1 transmission, of which bovine lactoferrin (bLF) is the most potent inhibitor. bLF binds strongly to DC-SIGN, thus preventing virus capture and subsequent transmission. Interestingly, bLF is a much more efficient inhibitor of transmission than human lactoferrin. Since bLF is nontoxic and easy to purify in large quantities, it is an interesting candidate microbicide against HIV-1. Another advantage of bLF is its ability to block HIV-1 replication in T cells. DC-mediated capture of a bLF-resistant HIV-1 variant that was selected during long-term culturing in T cells could still be blocked by bLF. This underscores the usefulness of bLF as a microbicide drug to prevent HIV-1 transmission.

Topics: Animals; Cattle; Cell Adhesion Molecules; Dendritic Cells; HIV Envelope Protein gp120; HIV Infections; HIV-1; Humans; In Vitro Techniques; Lactoferrin; Lectins, C-Type; Protein Binding; Receptors, Cell Surface; Species Specificity; Virus Replication

Sexual contact with HIV-infected semen is a major driving force behind the global HIV pandemic. Little is known regarding the immune correlates of virus shedding in this compartment, although HIV-1-specific CD8+ T cells are present in semen. We collected blood and semen from 27 chronically HIV-infected, therapy-naive men without common sexually transmitted infections or urethral inflammation and measured HIV-1 RNA viral load and cytokine/chemokine levels in both compartments. HIV-1 RNA levels were 10-fold higher in blood than semen, but discordantly high semen shedding was associated with higher semen levels of the proinflammatory cytokines IL-6, IL-8, IL-12, and IFN-gamma. Virus-specific CD8+ T cell epitopes were mapped in blood by IFN-gamma ELISPOT, using an overlapping HIV-1 clade B peptide matrix, and blood and semen CD8+ T cell responses were then assayed ex vivo using intracellular IFN-gamma staining. HIV-specific CD8+ responses were detected in 70% of semen samples, and their frequency was similar to or higher than blood. There was no correlation between the presence of virus-specific CD8+ T cells in semen and levels of HIV-1 RNA shedding. Among participants with detectable CD8+ IFN-gamma semen responses, their relative frequency was not associated with reduced HIV-1 RNA shedding, and their absolute number was correlated with higher levels of HIV-1 RNA semen shedding (r = 0.6; p = 0.03) and of several proinflammatory cytokines. Neither the presence nor the frequency of semen HIV-specific CD8+ T cell IFN-gamma responses in semen correlated with reduced levels of HIV RNA in semen.

Topics: CD8-Positive T-Lymphocytes; Cytokines; Epitopes, T-Lymphocyte; HIV Infections; HIV-1; Humans; Interferon-gamma; Lactoferrin; Male; Proteinase Inhibitory Proteins, Secretory; Proteins; RNA, Viral; Semen; Virus Shedding

The aim of this study was to explore lysozyme and lactoferrin concentrations in human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis (OPC). These proteins were measured by time-resolved immunofluorometric assay, validated in Part I of this study, in paired serum and salivary secretions of 30 patients. Eleven HIV-positive patients without OPC, eight HIV-positive patients with OPC and eleven HIV-negative healthy subjects were included in the study. The relative coefficient of excretion of salivary albumin was used to establish protein origin. In serum, the low lactoferrin concentrations in HIV-infected patients with and without OPC (0.610 mg/l (p < 0.05) and 0.896 mg/l (p < 0.01) vs. 1.439 mg/l in healthy subjects) were probably due to a decrease in nonspecific immunity, particularly the polymorphonuclear cells. In HIV-infected patients with OPC, the high salivary lysozyme and lactoferrin concentrations (170.94 mg/l and 66.48 mg/l vs. 23.35 mg/l and 10.20 mg/l in healthy subjects, respectively) and their mean relative coefficient of excretion of above 1 indicated a high local production of lysozyme and lactoferrin in saliva. The development of OPC in HIV-infected patients could be a consequence of inefficient lysozyme and lactoferrin concentrations and of decreased cooperation between innate and adaptative immune systems.

Topics: Candidiasis, Oral; Female; Fluoroimmunoassay; HIV Infections; Humans; Lactoferrin; Male; Mucous Membrane; Muramidase; Reference Standards; Saliva; Sensitivity and Specificity; Time Factors

Human T cell leukemia virus type I (HTLV-I) and HIV-1, causative agents of adult T cell leukemia/lymphoma and AIDS, respectively, are transmitted vertically via breast milk. Here we demonstrate that lactoferrin, a milk protein that has a variety of antimicrobial and immunomodulatory activities, facilitates replication of HTLV-I in lymphocytes derived from asymptomatic HTLV-I carriers and transmission to cord blood lymphocytes in vitro. Transient expression assays revealed that lactoferrin can transactivate HTLV-I long terminal repeat promoter. In contrast, lactoferrin inhibits HIV-1 replication, at least in part, at the level of viral fusion/entry. These results suggest that lactoferrin may have different effects on vertical transmission of the two milk-borne retroviruses.

Topics: Adjuvants, Immunologic; Antiviral Agents; Cells, Cultured; Coculture Techniques; HIV Infections; HIV-1; Human T-lymphotropic virus 1; Humans; Infectious Disease Transmission, Vertical; Lactoferrin; Membrane Fusion; Promoter Regions, Genetic; Retroviridae Infections; Terminal Repeat Sequences; Trans-Activators; Virus Replication

HIV-1 infection is associated with a dramatic reduction in antioxidative molecules both at the cellular level and in the circulation. This is particularly so for lactoferrin, an iron-binding protein involved in natural defenses (antimicrobial and antiviral activities, etc.) and found in whole secretions, including milk and mucus. In addition to its ability to chelate iron ions, lactoferrin inhibits hydroxy radical formation and interacts with nitric oxide (NO). Levels of plasma lactoferrin decreased in HIV-1-infected patients in correlation with progression of the disease, and highly specific anti-lactoferrin autoantibodies increased. This profile was specific to HIV-1 infection; it was not found in HIV-2-infected patients. In parallel with the drop in lactoferrin, a marked increase in circulating nitrogen derivatives was observed in HIV-1-infected patients, whereas low levels were found in normal donors and in HIV-2-infected patients. These data suggested hyperstimulation of the NO pathway throughout HIV-1 but not HIV-2 infection. This overproduction of NO could play an important role in the development of AIDS symptoms and signs.

Topics: Antibodies, Antineutrophil Cytoplasmic; CD4 Lymphocyte Count; Disease Progression; Enzyme-Linked Immunosorbent Assay; HIV Infections; HIV Seropositivity; HIV-1; HIV-2; Humans; Lactoferrin; Nitric Oxide; Nitrites

The aim of the present work was to determine the concentrations of iron and iron-binding proteins in the lungs of patients suffering from Pneumocystis carinii (PCP), which is crucial for justifying the treatment with iron-chelating agents in this disease.. Bronchoalveolar lavage was performed in 10 HIV patients with PCP and five healthy controls. Total iron and iron-binding proteins (transferrin, ferritin and lactoferrin) were measured in acellular bronchoalveolar lavage fluid (BALF) in both groups. Iron was determined by atomic absorption spectrometry; transferrin and lactoferrin were measured using specific enzyme-linked immunosorbent assays (ELISA); and ferritin concentration was quantified by automated immunonephelometry.. Our findings in patients with PCP demonstrated a six- to seven-fold increase of total iron levels and an eight-fold increase of ferritin in bronchoalveolar lavage fluid when compared with controls. No significant differences were found in transferrin or lactoferrin levels. Moreover, our results suggest that this iron is non-transferrin bound.. Non-transferrin bound iron is increased in the lower respiratory tracts of PCP patients. This finding would lend experiment support to the use of iron-chelating agents in this disease.

Topics: Adult; AIDS-Related Opportunistic Infections; Bronchoalveolar Lavage Fluid; Enzyme-Linked Immunosorbent Assay; Female; Ferritins; HIV Infections; Humans; Iron; Iron Chelating Agents; Lactoferrin; Lung; Male; Pneumonia, Pneumocystis; Spectrophotometry, Atomic; Transferrin

Topics: Animals; Cattle; Cells, Cultured; Drug Synergism; Female; HIV Infections; HIV-1; Humans; Lactoferrin; Leukocytes, Mononuclear; Pregnancy; Pregnancy Complications, Infectious; Reverse Transcriptase Inhibitors; Virus Replication; Zidovudine

Topics: Adult; Biomarkers; Female; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Lactoferrin; Maternal-Fetal Exchange; Pregnancy

Lactoferrin is a mammalian iron-binding glycoprotein present in many biological secretions, such as milk, tears, semen and plasma and a major component of the specific granules of polymorphonuclear leucocytes. The effect of bovine lactoferrin (BLf) in apo-form or saturated with ferric, manganese or zinc ions, on human immunodeficiency virus type 1 (HIV-1) infection in the C8166 T-cell line was studied. Both HIV-1 replication and syncytium formation were efficiently inhibited, in a dose-dependent manner, by lactoferrins. BLf in apo and saturated forms markedly inhibited HIV-1 replication when added prior to HIV infection or during the virus adsorption step, thus suggesting a mechanism of action on the HIV binding to or entry into C8166 cells. Likewise, the addition of Fe3+BLf prior to HIV infection and during the attachment step resulted in a marked reduction of the HIV-1 DNA in C8166 cells 20 h after infection. The potent antiviral effect and the high selectivity index exhibited by BLf suggest for this protein, in apo or saturated forms, an important role in inhibiting the early HIV-cell interaction, even though a post adsorption effect cannot be ruled out.

Topics: Adsorption; Animals; Anti-HIV Agents; Apoproteins; Cattle; Cell Line; Cytopathogenic Effect, Viral; DNA, Viral; Dose-Response Relationship, Drug; HIV Infections; HIV-1; Humans; Lactoferrin; Metals; Virus Replication

Paired sera and cervicovaginal secretions (CVS) from 30 women infected with human immunodeficiency virus (HIV) type 1 (before AIDS) were analyzed for IgG and IgA antibodies to HIV and for IgG, IgA, and human serum albumin. Subjects were compared with 30 aged-matched healthy controls. In HIV-infected women, cervicovaginal immunoglobulins were markedly increased, and IgG predominated. An increased immunoglobulin transudation was implicated, since cervicovaginal albumin levels were 2.3-fold above those of normal controls. Furthermore, IgG excretion by reference to albumin was increased 1.9-fold, whereas the IgA secretion tended to decrease, suggesting a possible enhanced local IgG synthesis. Mean IgG and IgA anti-HIV antibody titers were, respectively, 30- and 12-fold higher in serum than in CVS, but their mean specific activities were higher in CVS than in serum, suggesting a local synthesis of both isotypes. The IgA antibody response to HIV remained poor compared with the strong IgG response.

Topics: Adolescent; Adult; Africa; Antibody Specificity; Cervix Uteri; Female; France; HIV Antibodies; HIV Infections; HIV-1; Humans; Immunoglobulin A; Immunoglobulin G; Lactoferrin; Middle Aged; Reference Values; Serum Albumin; Vagina

Sera from 85 HIV-infected patients were tested for the presence of antilactoferrin antibodies (anti-LF Abs) by specific ELISA. Fifty-seven sera were found positive, including sera from asymptomatic (18/28, 64.3%, mean O.D.: 0.27 +/- 0.05) and symptomatic patients (39/57, 68.4%, mean O.D.: 0.82 +/- 0.15). In the control group, only one out of 26 normal donors show any reactivity (mean O.D.: 0.06 +/- 0.01). None of the tested patients had clinical evidence of vasculitis, the previous reported antilactoferrin-associated pathology and if, in both groups, a similar frequency of anti-LF Abs was found, the autoantibody level was significantly higher among the symptomatic patients (p < 0.01). However, correlation was found neither with polymorphonuclear cell counts nor with the level of circulating lactoferrin. The characterization and the clinical significance of the autoantibodies are under investigation.

Topics: Acquired Immunodeficiency Syndrome; Autoantibodies; Blotting, Western; Enzyme-Linked Immunosorbent Assay; HIV Infections; HIV Seropositivity; Humans; Lactoferrin

Lactoferrin, lysozyme, interferon, and neopterin levels were determined in parotid saliva from 44 individuals with different clinical stages of human immunodeficiency virus (HIV) infection and 19 HIV-seronegative controls. The secretory output of individual components was calculated according to the fluid flow rate. No parotid interferon activity was found in any of the HIV-infected subjects or controls, and no significant differences in parotid lysozyme or neopterin outputs were observed. The lactoferrin output was significantly decreased in HIV-seropositive subjects in parallel with their markedly reduced parotid secretory IgA output. This combined deficiency of parotid lactoferrin and secretory IgA may well contribute to the frequent oral infections seen in subjects with HIV infection.

Topics: Adult; Biopterins; HIV Infections; Humans; Interferons; Lactoferrin; Male; Mouth Diseases; Muramidase; Neopterin; Parotid Gland; Saliva

Parotid flow rate and chemistry of 78 HIV + gay/bisexual men and 27 HIV-gay/bisexual controls were compared on a longitudinal basis at 4-month intervals over a 1 yr period for changes indicative of inflammatory or autoimmune diseases of the salivary glands, or reduced protective capacity toward oral opportunistic infection. Parotid saliva was examined for concentrations of sodium, chloride, phosphate, total protein, lysozyme, lactoferrin, secretory IgA, salivary peroxidase, histatin and albumin. Chloride, lysozyme and peroxidase were significantly higher in HIV + at all 3 examinations and increased in concentration over time. Although mean values for stimulated flow rate were not significantly different in the two groups over the year, there was a significant increase in the number of HIV + with reduced flow over time. In 6% of HIV + there was a marked reduction in flow rate and Sjögren's syndrome-like elevations in parotid chemistry but no enlargement. At all examinations low flow rate was significantly related to oral candidiasis; T4 levels were inversely related to oral candidiasis, but not to concentration of salivary components or flow rate; nor was AZT use. As a group the HIV + patients maintained normal flow rate and secreted normal or elevated concentrations of protective proteins. A subgroup, however, exhibited diminished flow over time and an increasing tendency to oral candidiasis and a diminution in output of histatins.

Topics: Adult; Bisexuality; Candidiasis, Oral; Chlorides; HIV Infections; HIV Seropositivity; HIV-1; Homosexuality; Humans; Lactoferrin; Longitudinal Studies; Male; Muramidase; Parotid Gland; Peroxidases; Saliva; Secretory Rate; Sodium

Parotid and submandibular gland function were evaluated in 12 HIV-1 antibody-positive men at two visits separated by a median interval of 14.5 months (range 6-22 months). Unstimulated and stimulated flow rates, and the concentrations of total protein, lysozyme, albumin and lactoferrin in these secretions, were determined. Parotid and submandibular gland secretions changed in a specific fashion with time. Lysozyme levels in both glandular stimulated secretions showed significant changes (approximately 40% and 70% elevated, between visits, in parotid and submandibular saliva, respectively). In addition, the frequency with which albumin was detected in unstimulated parotid secretions increased with time. These findings support earlier results suggesting the presence of alterations in major salivary gland function following HIV-1 infection. Submandibular gland function appears to manifest these alterations earlier, but with time the parotid secretions show similar changes.

Topics: Albumins; HIV Infections; Humans; Lactoferrin; Longitudinal Studies; Male; Muramidase; Saliva; Salivary Glands; Salivary Proteins and Peptides; Secretory Rate