lipoteichoic-acid and Bacterial-Infections

Wall teichoic acid (WTA) and lipoteichoic acid (LTA) are structural components of Gram-positive bacteria's peptidoglycan and cell membrane, which are mostly anionic glycopolymers. WTA confers numerous physiological, virulence, and pathogenic features to bacterial pathogens. It controls cell shape, cell division, and the localisation of autolytic enzymes and ion homeostasis. In the context of virulence and pathogenicity, it aids bacterial cell attachment and colonisation and protects against the host defence system and antibiotics. Having such a broad function in pathogenic bacteria's lifecycle, WTA/LTA become one of the potential targets for antibacterial agents to reduce bacterial infection in the host. The number of reports for targeting the WTA/LTA pathway has risen, mostly by focusing on three distinct targets: antivirulence targets, β-lactam potentiator targets, and essential targets. The current review looked at the role of WTA/LTA in biofilm development and virulence in a range of Gram-positive pathogenic bacteria. Furthermore, alternate strategies, such as the application of natural and synthetic compounds that target the WTA/LTA pathway, have been thoroughly discussed. Moreover, the application of nanomaterials and a combination of drugs have also been discussed as a viable method for targeting the WTA/LTA in numerous Gram-positive bacteria. In addition, a future perspective for controlling bacterial infection by targeting the WTA/LTA is proposed.

Topics: Anti-Bacterial Agents; Bacterial Infections; Biofilms; Cell Wall; Gram-Positive Bacteria; Humans; Lipopolysaccharides; Teichoic Acids; Virulence

Recent studies have demonstrated that human dental pulp cells sense pathogens and elicit innate and/or adaptive immunity. Particular attention has been paid to odontoblasts that are situated at the pulp-dentin interface and constitute the first line of defense to cariogenic bacteria entering dentin after enamel disruption. In this review, recent in vitro and in vivo data suggesting that odontoblasts initiate immune/inflammatory events within the dental pulp in response to cariogenic bacteria are discussed. These data include sensing of pathogens by Toll-like receptors (TLRs), production of chemokines upon cell stimulation with microbial by-products and induction of dendritic cell migration. Additional results presented here reveal that all TLR genes are expressed in the healthy human dental pulp that is thus well equipped to combat pathogens entering the tissue. Seventeen chemokine genes including CXCL12, CCL2, CXCL9, CX3CL1, CCL8, CXCL10, CCL16, CCL5, CXCL2, CCL4, CXCL11 and CCL3, and 9 chemokine receptor genes including CXCR4, CCR1, CCR5, CX3CR1, CCR10 and CXCR3, are also expressed in pulp. TLR2, CCL2 and CXCL1 are upregulated in odontoblasts both under caries lesions and upon stimulation with pathogen by-products. These molecules thus appear as preferential targets for the design of therapeutic agents able to reduce the immune/inflammatory response to cariogenic bacteria and favor pulp healing.

Topics: Bacterial Infections; Chemokines; Conserved Sequence; Dental Caries; Dental Pulp; Humans; Lipopolysaccharides; Molar; Odontoblasts; Receptors, Chemokine; Teichoic Acids; Toll-Like Receptors; Tooth Diseases

Various bacterial components (e.g., endotoxin, teichoic and lipoteichoic acids, peptidoglycans, DNA) induce or enhance inflammation by stimulating the innate immune system and/or are directly toxic in eukariotic cells (e.g., hemolysins). When antibiotics which inhibit bacterial protein synthesis kill bacteria, smaller quantities of proinflammatory or toxic compounds are released in vitro and in vivo than during killing of bacteria by beta-lactams and other cell-wall active drugs. In general, high antibiotic concentrations liberate lower quantities of bacterial proinflammatory or toxic compounds than concentrations close to the minimum inhibitory concentration. In animal models of Escherichia coli Pseudomonas aeruginosa and Staphylococcus aureus peritonitis/sepsis and of Streptococcus pneumoniae meningitis, a lower release of proinflammatory bacterial compounds was associated with a reduced mortality or neuronal injury. Pre-treatment with a bacterial protein synthesis inhibitor reduced the strong release of bacterial products usually observed during treatment with a beta-lactam antibiotic. Data available strongly encourage clinical trials comparing antibiotic regimens with different release of proinflammatory/toxic bacterial products. The benefit of the approach to reduce the liberation of bacterial products should be greatest in patients with a high bacterial load.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Bacterial Proteins; Bacterial Toxins; DNA, Bacterial; Humans; Immunity, Innate; Immunologic Factors; In Vitro Techniques; Inflammation Mediators; Lipopolysaccharides; Protein Synthesis Inhibitors; Teichoic Acids

The alarming increase in drug-resistant bacteria makes a search for novel means of fighting bacterial infections imperative. An attractive approach is the use of agents that interfere with the ability of the bacteria to adhere to tissues of the host, since such adhesion is one of the initial stages of the infectious process. The validity of this approach has been unequivocally demonstrated in experiments performed in a wide variety of animals, from mice to monkeys, and recently also in humans. Here we review various approaches to anti-adhesion therapy, including the use of receptor and adhesin analogs, dietary constituents, sublethal concentrations of antibiotics and adhesin-based vaccines. Because anti-adhesive agents are not bactericidal, the propagation and spread of resistant strains is much less likely to occur than as a result of exposure to bactericidal agents, such as antibiotics. Anti-adhesive drugs, once developed, may, therefore, serve as a new means to fight infectious diseases.

Topics: Adhesins, Bacterial; Animals; Anti-Bacterial Agents; Bacterial Adhesion; Bacterial Infections; Bacterial Vaccines; Carbohydrate Metabolism; Carbohydrates; Humans; Hyaluronic Acid; Immunity, Innate; Lipopolysaccharides; Peptides; Teichoic Acids; Vaccination

Lipoteichoic acid (LTA) is a surface-associated adhesion amphiphile from Gram-positive bacteria and regulator of autolytic wall enzymes (muramidases). It is released from the bacterial cells mainly after bacteriolysis induced by lysozyme, cationic peptides from leucocytes, or beta-lactam antibiotics. It binds to target cells either non-specifically, to membrane phospholipids, or specifically, to CD14 and to Toll-like receptors. LTA bound to targets can interact with circulating antibodies and activate the complement cascade to induce a passive immune kill phenomenon. It also triggers the release from neutrophils and macrophages of reactive oxygen and nitrogen species, acid hydrolases, highly cationic proteinases, bactericidal cationic peptides, growth factors, and cytotoxic cytokines, which may act in synergy to amplify cell damage. Thus, LTA shares with endotoxin (lipopolysaccharide) many of its pathogenetic properties. In animal studies, LTA has induced arthritis, nephritis, uveitis, encephalomyelitis, meningeal inflammation, and periodontal lesions, and also triggered cascades resulting in septic shock and multiorgan failure. Binding of LTA to targets can be inhibited by antibodies, phospholipids, and specific antibodies to CD14 and Toll, and in vitro its release can be inhibited by non-bacteriolytic antibiotics and by polysulphates such as heparin, which probably interfere with the activation of autolysis. From all this evidence, LTA can be considered a virulence factor that has an important role in infections and in postinfectious sequelae caused by Gram-positive bacteria. The future development of effective antibacteriolitic drugs and multidrug strategies to attenuate LTA-induced secretion of proinflammatory agonists is of great importance to combat septic shock and multiorgan failure caused by Gram-positive bacteria.

Topics: Adhesins, Bacterial; Animals; Arthritis; Bacterial Infections; Bacteriolysis; Cytokines; Disease Models, Animal; Drosophila Proteins; Encephalomyelitis; Gram-Positive Bacteria; Humans; Lipopolysaccharide Receptors; Lipopolysaccharides; Macrophages; Membrane Glycoproteins; Nephritis; Neutrophils; Reactive Oxygen Species; Receptors, Cell Surface; Teichoic Acids; Toll-Like Receptors; Uveitis; Virulence

Topics: Animals; Antigens, Bacterial; Bacterial Infections; Bacterial Proteins; Fibronectins; Fimbriae, Bacterial; Humans; Lipopolysaccharides; Phagocytosis; Phosphatidic Acids; Receptors, Fibronectin; Receptors, Immunologic; Receptors, Virus; Species Specificity; Teichoic Acids; Virulence

Topics: Animals; Antibodies, Bacterial; Bacteria; Bacterial Infections; Cell Membrane; Cell Wall; Erythrocytes; Humans; Kinetics; Lipopolysaccharides; Lymphocytes; Phosphatidic Acids; Receptors, Drug; Sepsis; Teichoic Acids

A review on the significance of the bacterial adherence of the host parasite-relationship. Special attention is drawn to the following topics: bacterial adhesion as a principle of pathogenicity, the specificity of the reaction, the nature of adhesion-receptors. Furthermore, the non specific mucosal defense and the possibilities of preventative measures are discussed.

Topics: Adhesiveness; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Bacteria; Bacterial Infections; Bacterial Physiological Phenomena; Bacterial Proteins; Bacterial Toxins; Fimbriae, Bacterial; Humans; Immunization; Lipopolysaccharides; Membrane Proteins; Mucous Membrane; Phagocytosis; Phosphatidic Acids; Teichoic Acids; Virus Physiological Phenomena

Recent studies have indicated that the attachment of bacteria to mucosal surfaces is the initial event in the pathogenesis of most infectious diseases due to bacteria in animals and humans. An understanding of the mechanisms of attachment and a definition of the adhesive molecules on the surfaces of bacteria (adhesins) as well as those on host cell membranes (receptors) have suggested new approaches to the prevention of serious bacterial infections: (1) application of purified adhesion or receptor materials or their analogues as competitive inhibitors of bacterial adherence; (2) administration of sublethal concentrations of antibiotics that suppress the formation and expression of bacterial adhesins; and (3) development of vaccines against bacterial surface components involved in adhesion to mucosal surfaces. Progress has already been made in the development of antiadhesive vaccines directed against the fimbrial adhesins of several human bacterial pathogens.

Topics: Adhesiveness; Animals; Bacterial Infections; Bacterial Physiological Phenomena; Bacterial Vaccines; Binding Sites; Epithelium; Escherichia coli; Female; Glycerophosphates; Humans; Lipid Metabolism; Lipopolysaccharides; Mouth Mucosa; Mucous Membrane; Phosphatidic Acids; Species Specificity; Streptococcus mutans; Streptococcus pyogenes; Streptococcus sanguis; Teichoic Acids

C-type lectins (CTLs) are important pathogen pattern recognition receptors that recognize carbohydrate structures. In present study, a C-type lectin domain family 4 member E-like gene from turbot, which tentatively named SmCLEC4E-like (SmCLEC4EL), was identified, and the expressional and functional analyses were performed. In our results, SmCLEC4EL showed conserved synteny with CLEC4E-like genes from several fish species in genome, and possessed a typical type II transmembrane CTL architecture: an N-terminal intracellular region, a transmembrane domain and a C-terminal extracellular region which contained a predicted carbohydrate recognition domain (CRD). In addition, SmCLEC4EL exhibited the highest expression level in spleen in healthy fish, and showed significantly induced expression in mucosal tissues, intestine and skin, under bacteria challenge. Finally, the recombinant SmCLEC4EL protein combined with LPS, PGN, LTA and five different kinds of bacteria in a dose-dependent manner, and agglutinated these bacteria strains in the presence of calcium. These findings collectively demonstrated that SmCLEC4EL, a calcium-dependent CTL, could function as a pattern recognition receptor in pathogen recognition and participate in host anti-bacteria immunity.

Topics: Amino Acid Sequence; Animals; Bacterial Infections; Fish Diseases; Fish Proteins; Flatfishes; Gene Expression Profiling; Gene Expression Regulation; Immunity, Innate; Lectins, C-Type; Lipopolysaccharides; Peptidoglycan; Phylogeny; Sequence Alignment; Teichoic Acids

(Aim) Bacterial infection underlies the pathogenesis of many human diseases, including acute and chronic inflammation. Here, we investigated a possible role for bacterial infection in the progression of chronic pancreatitis. (Materials and Methods) Pancreatic juice was obtained from patients with pancreatic cancer (n = 20) or duodenal cancer/bile duct cancer (n = 16) and subjected to PCR using universal primers for the bacterial 16S ribosomal RNA gene. Bacterial species were identified by PCR using bile samples from four pancreatic cancer patients. PCR products were subcloned into T-vectors, and the sequences were then analyzed. Immunohistochemical and serologic analyses for Enterococcus faecalis infection were performed on a large cohort of healthy volunteers and patients with chronic pancreatitis or pancreatic cancer and on mice with caerulein-induced chronic pancreatitis. The effect of E. faecalis antigens on cytokine secretion by pancreatic cancer cells was also investigated. (Results) We found that 29 of 36 pancreatic juice samples were positive for bacterial DNA. Enterococcus and Enterobacter species were detected primarily in bile, which is thought to be a pathway for bacterial infection of the pancreas. Enterococcus faecalis was also detected in pancreatic tissue from chronic pancreatitis and pancreatic cancer patients; antibodies to E. faecalis capsular polysaccharide were elevated in serum from chronic pancreatitis patients. Enterococcus-specific antibodies and pancreatic tissue-associated E. faecalis were detected in mice with caerulein-induced chronic pancreatitis. Addition of Enterococcus lipoteichoic acid and heat-killed bacteria induced expression of pro-fibrotic cytokines by pancreatic cancer cells in vitro. (Conclusion) Infection with E. faecalis may be involved in chronic pancreatitis progression, ultimately leading to development of pancreatic cancer.

Topics: Adenocarcinoma; Animals; Antibodies, Bacterial; Bacterial Infections; Disease Models, Animal; Enterococcus; Female; Gene Expression Regulation, Neoplastic; Hot Temperature; Humans; Interleukin-8; Lipopolysaccharides; Male; Middle Aged; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis, Chronic; RNA, Messenger; RNA, Ribosomal, 16S; Teichoic Acids; Vascular Endothelial Growth Factor A

Bacterial translocation is associated with clinically relevant complications in cirrhosis. We evaluated the effect of toll-like receptor polymorphisms in the soluble response against these episodes. Consecutive patients with cirrhosis and ascitic fluid were distributed by TLR2 rs4696480, TLR4 rs4986790, and TLR9 rs187084 single-nucleotide polymorphisms. Lipoteichoic acid, lipopolyssaccharide, bacterial-DNA, pro-inflammatory cytokines and nitric oxide levels were quantified in serum samples. In vitro response against specific ligands in variant TLR genotypes was evaluated. One hundred and fourteen patients were included. Variant TLR-2, TLR-4 and TLR-9 SNP genotypes were associated with significantly increased serum levels of LTA, LPS and bacterial-DNA. TNF-α, IL-6 and nitric oxide serum levels were significantly decreased in all variant TLR genotyped patients. Cytokine levels were significantly less upregulated in response to specific TLR-ligands in patients with all variant vs wildtype TLR genotypes. Although in vitro gene expression levels of all wildtype and variant TLRs were similar, MyD88 and NFkB were significantly downregulated in cells from TLR-variant genotyped patients in response to their ligands. Variant TLR genotypes are associated with an increased circulating antigen burden and a decreased proinflammatory response in cirrhosis. This immunodeficiency may facilitate bacteria-related complications in cirrhosis and enhance TLR targeting for its management.

Topics: Aged; Bacterial Infections; Cytokines; DNA, Bacterial; Female; Humans; Lipopolysaccharides; Liver Cirrhosis; Male; Middle Aged; Nitric Oxide; Polymorphism, Single Nucleotide; Prospective Studies; Teichoic Acids; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptor 9

The Acute Respiratory Distress Syndrome (ARDS), remains a significant source of morbidity and mortality in critically ill patients. Pneumonia and sepsis are leading causes of ARDS, the pathophysiology of which includes increased pulmonary microvascular permeability and hemodynamic instability resulting in organ dysfunction. We hypothesized that N-ethylmaleimide sensitive factor (NSF) regulates exocytosis of inflammatory mediators, such as Angiopoietin-2 (Ang-2), and cytoskeletal stability by modulating myosin light chain (MLC) phosphorylation. Therefore, we challenged pulmonary cells, in vivo and in vitro, with Gram Positive bacterial cell wall components, lipoteichoic acid (LTA), and peptidoglycan (PGN) and examined the effects of NSF inhibition.. Mice were pre-treated with an inhibitor of NSF, TAT-NSF700 (to prevent Ang-2 release). After 30min, LTA and PGN (or saline alone) were instilled intratracheally. Pulse oximetry was assessed in awake mice prior to, and 6 hour post instillation. Post mortem, tissues were collected for studies of inflammation and Ang-2. In vitro, pulmonary endothelial cells were assessed for their responses to LTA and PGN.. Pulmonary challenge induced signs of airspace and systemic inflammation such as changes in neutrophil counts and protein concentration in bronchoalveolar lavage fluid and tissue Ang-2 concentration, and decreased physiological parameters including oxygen saturation and pulse distention. TAT-NSF700 pre-treatment reduced LTA-PGN induced changes in lung tissue Ang-2, oxygen saturation and pulse distention. In vitro, LTA-PGN induced a rapid (<2 min) release of Ang-2, which was significantly attenuated by TAT-NSF700 or anti TLR2 antibody. Furthermore, TAT-NSF700 reduced LTA-PGN-induced MLC phosphorylation at low concentrations of 1-10 nM.. TAT-NSF700 decreased Ang-2 release, improved oxygen saturation and pulse distention following pulmonary challenge by inhibiting MLC phosphorylation, an important component of endothelial cell retraction. The data suggest that inhibition of NSF in pneumonia and sepsis may be beneficial to prevent the pulmonary microvascular and hemodynamic instability associated with ARDS.

Topics: Angiopoietin-1; Animals; Bacterial Infections; Blood Vessels; Cell Line; Cell Wall; Cytoskeleton; Disease Models, Animal; Exocytosis; Gram-Positive Bacteria; Humans; Inflammation; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred BALB C; Microcirculation; N-Ethylmaleimide-Sensitive Proteins; Oxygen; Peptidoglycan; Phosphorylation; Pneumonia; Respiratory Distress Syndrome; Sepsis; Teichoic Acids; Vascular Diseases

Hagfish C1q (HaC1q) was identified and characterized as a pattern-recognition molecule (PRM) in the hagfish complement system. The serum from hagfish, Eptatretus burgeri, was applied to a GlcNAc-agarose column and eluted sequentially with GlcNAc and EDTA. Four (31, 27, 26, and 19 kDa) and one (26 kDa) proteins were detected as bound molecules in the GlcNAc- and the EDTA-eluates, respectively. Among these, the 26 kDa protein from the EDTA eluate was found to be a homologue of mammalian C1q through cDNA analysis. HaC1q had an ability to bind to various microbes in a Ca(2+)-dependent manner and its target ligands on the microbes were lipopolysaccharide, lipoteichoic acid, and peptidoglycan. The binding of HaC1q to GlcNAc-agarose was not inhibited by an excess amount of monosaccharide such as GlcNAc. While HaC1q bound to Sepharose 6B with a matrix of GlcNAc-agarose (polymer of agarobiose), it did not bind to Sepharose 4B that contained lower concentration of agarobiose than Sepharose 6B. Therefore, the target of HaC1q on GlcNAc-agarose was concluded to be agarobiose and high density of the target moiety seemed to be required for the stable binding. This finding was in accordance with the known behavior of other lectins involved in the complement system. We have concluded that HaC1q recognizes agarobiose-like structures present on the surface of microbes and acts as a pattern-recognition molecule in the process for elimination of invading microbes.

Topics: Amino Acid Sequence; Animals; Bacterial Infections; Calcium; Complement C1q; Disaccharides; Hagfishes; Immunity, Innate; Lipopolysaccharides; Mammals; Molecular Sequence Data; Peptidoglycan; Protein Binding; Receptors, Pattern Recognition; Teichoic Acids

Interleukin (IL)-17-producing T cells play a critical role in the immune response against microbial pathogens. Traditionally, experimental studies have focused upon understanding the activity of IL-17-producing T cells which differentiate from naive T cells in the peripheral immune system. However, we have demonstrated previously that IL-17-producing T cells are also present in the thymus of naive wild-type mice and can be co-activated there by microbial stimuli. Other studies have supported the concept that IL-17-producing thymocytes have a specific role in the immediate defence against microbial pathogens, which is independent from the development of an adaptive immune response. Given an important role of the thymus in systemic bacterial infection and sepsis, in this study we investigate the effect of a broad spectrum of bacteria and cell wall components on thymocyte cytokine production. Surprisingly, we find that all types of bacteria investigated (including non-pathogenic species) uniformly activate IL-17-producing thymocytes upon α-CD3 stimulation. In contrast, there is a heterogeneous effect on IL-6 and interferon (IFN)-γ-production with Gram-negative bacteria inducing far higher frequencies of IL-6- and IFN-γ-producing thymocytes than Gram-positive bacteria. We conclude that IL-17-producing thymocytes constitute a 'first line of recognition', but not a 'first line of defence' against bacteria in general. Their activity might lead to immune activation, but not necessarily to a pathological inflammatory disease condition. The difference between these two states might be determined by other immunological effector molecules, such as IL-6 and IFN-γ.

Topics: Animals; Bacterial Infections; CD4-Positive T-Lymphocytes; Cell Wall; Female; Inflammasomes; Interferon-gamma; Interleukin-17; Interleukin-6; Lipopolysaccharides; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Peptidoglycan; Teichoic Acids; Thymocytes; Toll-Like Receptor 2

The avian eggshell membranes are essential elements in the fabrication of the calcified shell as a defense against bacterial penetration. Ovocalyxin-36 (OCX-36) is an abundant avian eggshell membrane protein, which shares protein sequence homology to bactericidal permeability-increasing protein (BPI), lipopolysaccharide-binding protein (LBP) and palate, lung and nasal epithelium clone (PLUNC) proteins. We have developed an efficient method to extract OCX-36 from chicken eggshell membranes for purification with cation and anion exchange chromatographies. Purified OCX-36 protein exhibited lipopolysaccharide (LPS) binding activity and bound lipopolysaccharide (LPS) from Escherichia coli O111:B4 in a dose-dependent manner. OCX-36 showed inhibitory activity against growth of Staphylococcus aureus ATCC 6538. OCX-36 single nucleotide polymorphisms (SNPs) were verified at cDNA 211 position and the corresponding proteins proline-71 (Pro-71) or serine-71 (Ser-71) were purified from eggs collected from genotyped hens. A significant difference between Pro-71 and Ser-71 OCX-36 for S. aureus lipoteichoic acid (LTA) binding activity was detected. The current study is a starting point to understand the innate immune role that OCX-36 may play in protection against bacterial invasion of both embryonated eggs (relevant to avian reproductive success) and unfertilized table eggs (relevant to food safety).

Topics: Acute-Phase Proteins; Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Bacteria; Bacterial Infections; Blood Proteins; Blotting, Western; Carrier Proteins; Cell Membrane; Chickens; Chromatography, Liquid; Egg Proteins; Enzyme-Linked Immunosorbent Assay; Lipopolysaccharides; Membrane Glycoproteins; Polymorphism, Single Nucleotide; Tandem Mass Spectrometry; Teichoic Acids

Metabolic alterations associated with diabetes mellitus alter innate immunity. Dogs often develop infectious or inflammatory complications related to diabetes mellitus, yet little is known about the effects of diabetes mellitus on the immune system in this species.. Prospective evaluation in dogs with poorly regulated spontaneous type 1 diabetes mellitus (T1DM). In vitro leukocyte cytokine response to lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PG) was compared between dogs with T1DM and healthy dogs. Additionally, the effect of acute in vitro glucose exposure on leukocyte tumor necrosis factor (TNF) production from healthy dogs was measured.. Leukocytes from dogs with T1DM had significantly greater TNF production after LTA and PG stimulation compared with leukocytes from healthy dogs. Leukocyte interleukin (IL)-6 production was greater after stimulation with LPS, LTA, PG, and phosphate-buffered saline in the T1DM group. No such difference was noted when evaluating IL-10 production between groups regardless of stimulant. Dogs with T1DM had significantly greater IL-6 to IL-10 production ratios than healthy dogs. Acute exposure to dextrose did not augment cytokine production from healthy canine leukocytes.. Dogs with T1DM have altered innate immunity characterized by upregulation of proinflammatory cytokine production without a concurrent change in anti-inflammatory cytokine production. This may be one explanation for the common infectious and inflammatory complications associated with T1DM in dogs.

Topics: Animals; Bacterial Infections; Blood Glucose; Case-Control Studies; Cytokines; Diabetes Mellitus, Type 1; Dog Diseases; Dogs; Female; Hypoglycemic Agents; Immunity, Innate; Inflammation; Inflammation Mediators; Insulin; Interleukin-10; Interleukin-6; Leukocytes; Lipopolysaccharides; Male; Peptidoglycan; Teichoic Acids; Tumor Necrosis Factor-alpha; Up-Regulation

The diagnosis of prosthetic joint infection and its differentiation from aseptic loosening remains problematic. The definitive laboratory diagnostic test is the recovery of identical infectious agents from multiple intraoperative tissue samples; however, interpretation of positive cultures is often complex as infection is frequently associated with low numbers of commensal microorganisms, in particular the coagulase-negative staphylococci (CNS). In this investigation, the value of serum procalcitonin (PCT), interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) as predictors of infection in revision hip replacement surgery is assessed. Furthermore, the diagnostic value of serum IgG to short-chain exocellular lipoteichoic acid (sce-LTA) is assessed in patients with infection due to CNS. Presurgical levels of conventional serum markers of infection including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) is also established. Forty-six patients undergoing revision hip surgery were recruited with a presumptive clinical diagnosis of either septic (16 patients) or aseptic loosening (30 patients). The diagnosis was confirmed microbiologically and levels of serum markers were determined. Serum levels of IL-6 and sICAM-1 were significantly raised in patients with septic loosening (P = 0.001 and P = 0.0002, respectively). Serum IgG to sce-LTA was elevated in three out of four patients with infection due to CNS. In contrast, PCT was not found to be of value in differentiating septic and aseptic loosening. Furthermore, CRP, ESR and WBC were significantly higher (P = 0.0001, P = 0.0001 and P = 0.003, respectively) in patients with septic loosening. Serum levels of IL-6, sICAM-1 and IgG to sce-LTA may provide additional information to facilitate the diagnosis of prosthetic joint infection.

Topics: Arthroplasty, Replacement, Hip; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Humans; Immunoglobulin G; Intercellular Adhesion Molecule-1; Interleukin-6; Lipopolysaccharides; Predictive Value of Tests; Prospective Studies; Prostheses and Implants; Prosthesis-Related Infections; Protein Precursors; Teichoic Acids

Insect immune system comprises of both humoral and cellular defenses. Nodulation is one of the major, yet very poorly understood cellular responses against microbial infections in insects. Through screening for novel immune genes from an Indian saturniid silkmoth Antheraea mylitta, we identified a protein up-regulated in hemolymph within minutes upon bacterial challenge. We have shown here, for first time, the involvement of this novel protein in mediating nodulation response against bacteria and hence designated it as Noduler. Noduler possessed a characteristic reeler domain found in several extracellular matrix vertebrate proteins. Noduler was shown in vitro to bind a wide range of bacteria, yeast, and also insect hemocytes. Furthermore, Noduler specifically bound LPS, lipotechoic acid, and beta-1, 3 glucan components of microbial cell walls. RNA-interference mediated knock-down of the Noduler resulted in significant reduction in the number of nodules and consequent increase in bacterial load in larval hemolymph. The results suggest that the Noduler is widely conserved and is involved in very early clearance of bacteria by forming nodules of hemocytes and bacterial complexes in insects. The results would promote further studies for understanding of the crucial but hitherto overlooked nodulation mechanism in insects and also provide cues for the study of similar mammalian proteins whose function is not understood.

Topics: Amino Acid Sequence; Animals; Bacterial Infections; Bombyx; Cell Wall; Hemocytes; Hemolymph; Insect Proteins; Lipopolysaccharides; Mammals; Molecular Sequence Data; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Teichoic Acids; Up-Regulation

Concurrent infections in patients with human immunodeficiency virus (HIV) infection stimulate HIV replication. Chemokine receptors CXCR4 and CCR5 can act as HIV coreceptors. The authors hypothesized that concurrent infection increases the HIV load through up-regulation of CXCR4 and CCR5. Using experimental endotoxemia as a model of infection, changes in HIV coreceptor expression were assessed in 8 subjects injected with lipopolysaccharide (LPS, 4 ng/kg). The expression of CXCR4 and CCR5 on CD4(+) T cells was increased 2- to 4-fold, 4 to 6 hours after LPS injection. In whole blood in vitro, LPS induced a time- and dose-dependent increase in the expression of CXCR4 and CCR5 on CD4(+) T cells. Similar changes were observed after stimulation with cell wall components of Mycobacterium tuberculosis (lipoarabinnomannan) or Staphylococcus aureus (lipoteichoic acid), or with staphylococcal enterotoxin B. LPS increased viral infectivity of CD4-enriched peripheral blood mononuclear cells (PBMCs) with a T-tropic HIV strain. In contrast, M-tropic virus infectivity was reduced, possibly because of elevated levels of the CCR5 ligand cytokines RANTES and MIP-1beta. LPS-stimulated up-regulation of CXCR4 and CCR5 in vitro was inhibited by anti-TNF and anti-IFN gamma. Incubation with recombinant TNF or IFN gamma mimicked the LPS effect. Anti-interleukin 10 (anti-IL-10) reduced CCR5 expression, without influencing CXCR4. In accordance, rIL-10 induced up-regulation of CCR5, but not of CXCR4. Intercurrent infections during HIV infection may up-regulate CXCR4 and CCR5 on CD4(+) T cells, at least in part via the action of cytokines. Such infections may favor selectivity of HIV for CD4(+) T cells expressing CXCR4. (Blood. 2000;96:2649-2654)

Topics: Adult; Antigens, Bacterial; Bacterial Infections; CD4-Positive T-Lymphocytes; Cell Wall; Cells, Cultured; Chemokine CCL4; Chemokine CCL5; Endotoxemia; Enterotoxins; Gene Expression Regulation; HIV Infections; HIV Seronegativity; HIV-1; Humans; Interferon-gamma; Interleukin-10; Lipopolysaccharides; Macrophage Inflammatory Proteins; Models, Biological; Mycobacterium tuberculosis; Receptors, CCR5; Receptors, CXCR4; Recombinant Proteins; Selection, Genetic; Staphylococcus aureus; Teichoic Acids; Tumor Necrosis Factor-alpha; Virus Replication

To determine whether cultured human decidual cells and chorion cells produce interleukin-10 (IL-10) after incubation with purified bacterial products.. Decidual cell cultures and chorion cell cultures were established by standard techniques. With confluence, monolayers of each culture were incubated with purified bacterial products, including various concentrations of lipopolysaccharide (LPS), lipid A, and lipoteichoic acid (LTA) for 16 hr in quadruplicate. Culture supernatants were collected and assayed for immunodetectable IL-10 by enzyme-linked immunoadsorbent assay (ELISA).. Both decidual cell cultures and chorion cell cultures produced significant quantities of IL-10 after stimulation with LPS, lipid A, and LTA. Cultures of decidual cells produced more IL-10 than did chorion cell cultures.. Our data indicate that both maternal decidual cells and fetally derived chorion cells can produce IL-10 after incubation with bacterial virulence factors. This finding contrasts with our previous findings in which chorion cells did not produce IL-10 after stimulation with IL-1 beta, suggesting that chorion cell production after incubation with bacterial products is independent of IL-1 beta. We speculate that the contribution of anti-inflammatory IL-10 production by human gestational tissues to the inflammatory process in these tissues may be overcome or abrogated by the pro-inflammatory process.

Topics: Bacterial Infections; Cells, Cultured; Chorion; Decidua; Female; Humans; Interleukin-10; Lipid A; Lipopolysaccharides; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Teichoic Acids

The ability of bacteria and bacterial products to modulate the expression of Fc gamma receptors and major histocompatibility complex (MHC) class II molecules in resting rat bone marrow-derived mononuclear phagocytes (BMM phi) was determined by means of flow cytometry (FCM). Binding of IgG via Fc gamma receptors was considerably enhanced by most microbial agents; bacterial lipopolysaccharide, lipoteichoic acid and some intact bacteria proved to be as active as interferon-gamma (IFN-gamma) and augmented binding of IgG via high- and low-affinity Fc gamma receptors. In contrast, expression of MHC class II molecules by BMM phi was only slightly affected by the microbial agents. Additional findings attest that resting unprimed rat BMM phi are able to respond directly to Gram-negative and Gram-positive bacteria and to some of their products with the expression of marked secretory [in particular tumour necrosis factor-alpha (TNF-alpha) and nitrite] and cellular activities (TNF-alpha-independent tumoricidal activity). This extensive, direct type of macrophage activation may substantially amplify the capability of these cells to cope with these infectious agents in first-line, non-specific host defence.

Topics: Animals; Antigens, Bacterial; Bacterial Infections; Bone Marrow; Cells, Cultured; Histocompatibility Antigens Class II; Immunoglobulin G; Lipopolysaccharides; Macrophage Activation; Macrophages; Rats; Rats, Inbred Strains; Receptors, IgG; Teichoic Acids

Lipoteichoic acids (LTA) released by gram-positive bacteria can spontaneously bind to mammalian cell surfaces. In the present study, erythrocytes (E) sensitized with pneumococcal LTA (LTA-E) were used as a model system to determine if LTA could render host cells susceptible to damage by autologous complement. Complement (C)-mediated lysis of LTA-E from normal rats and normal humans occurred when these cells were incubated in their respective autologous sera in vitro. In addition, when LTA-E from a C2-deficient human and from C4-deficient guinea pigs were incubated in their autologous sera, there was significant lysis in vitro, demonstrating a role for the alternative pathway. The in vivo survival of 51Cr-labeled autologous LTA-E was also studied. Only 2.9% of autologous LTA-E remained in the circulation of normal rats after 90 min. In contrast, 31.2% of autologous LTA-E remained in the circulation of rats depleted of C3. Intravascular hemolysis accounted for the clearance of LTA-E in the normal rats, whereas liver sequestration was responsible for clearance in the C3-depleted rats. These results demonstrate that LTA can render the host's cells susceptible to damage by its own complement system, establishing this as a possible mechanism of tissue damage in natural bacterial infections.

Topics: Animals; Bacterial Infections; Complement Activation; Complement System Proteins; Egtazic Acid; Elapid Venoms; Guinea Pigs; Hemolysis; Humans; Lipopolysaccharides; Male; Phosphatidic Acids; Rats; Rats, Inbred Strains; Teichoic Acids

This study was performed to determine whether antibody-dependent cellular cytotoxicity (ADCC) could be directed against mammalian cells sensitized with spontaneously adhering bacterial substances. 51Cr-labeled SB leukemia cells were incubated with purified S43 group A streptococcal lipoteichoic acid (LTA; 0.001 to 100 micrograms/ml). Purified leukocyte ADCC effector cells were added to the LTA-coated target cells at various effector-to-target ratios (100:1 to 12:1), followed by the addition of rabbit anti-LTA. After incubation for 4 h, target cell lysis was calculated based on the release of label into the medium. As little as 1 ng of LTA per ml was sufficient to sensitize the target cells to ADCC lysis (12%); however, concentrations above 0.1 micrograms/ml generally resulted in 60 to 80% lysis. LTA alone was not cytotoxic to these target cells. Targeting did not occur if effector cells were sensitized or if free LTA was added to the medium. Specificity was demonstrated by cold-target inhibition, which showed that anti-LTA cytotoxicity could be inhibited only by unlabeled, LTA-treated target cells but not by cold SB cells alone. The findings indicate that certain soluble bacterial components, when bound to mammalian cells in the presence of specific antibody, can target ADCC effectors to these cells. This mechanism may be an important factor in the delayed sequelae of bacterial infections.

Topics: Adolescent; Adult; Antibodies; Antibody-Dependent Cell Cytotoxicity; Bacterial Infections; Female; Humans; Lipopolysaccharides; Male; Middle Aged; Neutrophils; Phosphatidic Acids; Teichoic Acids