lactoferrin and Disease-Resistance

The liver is a frontline immune site specifically designed to check and detect potential pathogens from the bloodstream to maintain a general state of immune hyporesponsiveness. One of the main functions of the liver is the regulation of iron homeostasis. The liver detects changes in systemic iron requirements and can regulate its concentration. Pathological states lead to the dysregulation of iron homeostasis which, in turn, can promote infectious and inflammatory processes. In this context, hepatic viruses deviate hepatocytes' iron metabolism in order to better replicate. Indeed, some viruses are able to alter the expression of iron-related proteins or exploit host receptors to enter inside host cells. Lactoferrin (Lf), a multifunctional iron-binding glycoprotein belonging to the innate immunity, is endowed with potent antiviral activity, mainly related to its ability to block viral entry into host cells by interacting with viral and/or cell surface receptors. Moreover, Lf can act as an iron scavenger by both direct iron-chelation or the modulation of the main iron-related proteins. In this review, the complex interplay between viral hepatitis, iron homeostasis, and inflammation as well as the role of Lf are outlined.

Topics: Animals; Biological Transport; Disease Resistance; Disease Susceptibility; Hepatitis, Viral, Human; Homeostasis; Host-Pathogen Interactions; Humans; Iron; Iron-Binding Proteins; Lactoferrin; Liver; Organ Specificity; Protein Binding; Receptors, Cell Surface

Recombinant proteins are currently recognized as pharmaceuticals, enzymes, food constituents, nutritional additives, antibodies and other valuable products for industry, healthcare, research, and everyday life. Lactoferrin (Lf), one of the promising human milk proteins, occupies the expanding biotechnological food market niche due to its important versatile properties. Lf shows antiviral, antimicrobial, antiprotozoal and antioxidant activities, modulates cell growth rate, binds glycosaminoglycans and lipopolysaccharides, and also inputs into the innate/specific immune responses. Development of highly efficient human recombinant Lf expression systems employing yeasts, filamentous fungi and undoubtedly higher plants as bioreactors for the large-scale Lf production is a biotechnological challenge. This review highlights the advantages and disadvantages of the existing non-animal Lf expression systems from the standpoint of protein yield and its biological activity. Special emphasis is put on the benefits of monocot plant system for Lf expression and the biosafety aspects of the transgenic Lf-expressing plants.

Topics: Animals; Disease Resistance; Fungi; Humans; Lactoferrin; Plants; Plants, Genetically Modified; Recombinant Proteins; Saccharomyces cerevisiae

The present study evaluated the growth performance, digestive enzyme activity, non-specific immunity, immunity and growth genes in Penaeus vannamei fed diets supplemented with Bovine lactoferricin (the basal diet without Bovine lactoferricin, the control; 1.0‰ Bovine lactoferricin，LCB1; 1.5‰ Bovine lactoferricin，LCB1.5; 2.0‰ Bovine lactoferricin, LCB2; 2.5‰ Bovine lactoferricin, LCB2.5) for 56 days. The feeding trial showed that the final weight, weight gain rate, and specific growth rate of the shrimp were improved significantly, while the feed conversion ratio was reduced significantly in the LCB1.5 group compared to the control (P < 0.05). The challenge test of Vibrio parahaemolyticus showed that the cumulative mortalities of shrimp in the LCB1.5, LCB2 and LCB2.5 groups were significantly lower than that in the control (P < 0.05). Compared with the control, Lipase and Trypsin activities in the hepatopancreas of LCB1.5 and LCB2 groups were significantly enhanced (P < 0.05). Compared with the control, alkaline phosphatase, acid phosphatase activities in the hepatopancreas and the relative expression levels of Relish, Toll, JAK, STAT, TOR, Raptor, 4E-BP, eIF4E1α, eIF4E2 genes in the hepatopancreas of LCB1.5, LCB2 and LCB2.5 groups were all significantly enhanced (P < 0.05). These results suggested that dietary Bovine lactoferricin could improve the growth performance, digestive capacity and immune responses of shrimp. When resistance against Vibrio parahaemolyticus in shrimp is considered, high dosage of Bovine lactoferricin showed a better effect than low dosage of Bovine lactoferricin. However, high dosage of Bovine lactoferricin can have a negative impact on the growth performance of shrimp. Considering collectively the above, Bovine lactoferricin could improve the growth performance, digestive enzymes activities, immune responses and disease resistance of P. vannamei.

Topics: Animal Feed; Animals; Diet; Disease Resistance; Immunity, Innate; Lactoferrin; Penaeidae; Vibrio parahaemolyticus

Lactoferrin is a multifunctional protein that has roles in iron metabolism, cell generation and differentiation, and antibacterial, antiviral, and antiparasitic activity. The study aim was to evaluate the effect of dietary lactoferrin powder on the innate immune response and disease resistance of silver carp (Hypophthalmichthys molitrix) infected with Vibrio vulnificus. The study also investigates immune cells in different organs including gills, intestine, spleen, liver, and pancreas using light, scan electron microcopy. Two diet regimes, a basic diet and a 600-mg/kg bovine lactoferrin-supplemented diet were used. The fish were fed for 30 successive days. We included 270 apparently healthy silver carp (H. Molitrix) with an average body weight of 10 ± 2 g/fish. Addition of lactoferrin to the diet led to an increase in the activity of non-specific immune parameters; lymphocytes, and in the monocytes percentage, and in total protein, serum globulin, and albumin, with a corresponding increase in phagocytic activities and indices. The histological analysis revealed increase immune cells such as lymphocytes in intestine, rodlet cells in liver, gills, and pancreas, and the macrophages in liver, pancreas as well as spleen. The lactoferrin-supplemented diet significantly increased survival and disease resistance following V. vulnificus challenge, which seemed to correspond to an enhancement of non-specific immune functions in H. molitrix. RESEARCH HIGHLIGHTS: The study evaluates the effect of dietary lactoferrin powder on the innate immune response and disease resistance of silver carp (Hypophthalmichthys molitrix) infected with Vibrio vulnificus. The study also investigates immune cells in different organs including gills, intestine, spleen, liver, and pancreas using light, scan electron microcopy. Lactoferrin increases the activity of nonspecific immune parameters; lymphocytes, and in the monocytes percentage, and in total protein, serum globulin, and albumin, with a corresponding increase in phagocytic activities and indices. The histological analysis revealed increase immune cells such as lymphocytes in intestine, rodlet cells in liver, gills, and pancreas, and the macrophages in liver, pancreas as well as spleen.

Topics: Albumins; Animals; Anti-Bacterial Agents; Antiparasitic Agents; Antiviral Agents; Carps; Disease Resistance; Electrons; Iron; Lactoferrin; Powders

The present study was carried out to investigate the effects of dietary bovine lactoferrin (BLF) or chitosan nanoparticles (CHN) alone or in combinations on serum biochemical indices, antioxidative capacity, transcriptomic responses, non-specific immunity, and resistance of Nile tilapia (Oreochromis niloticus) against challenge with Aeromonas hydrophila. Fish were fed on the basal diet with no supplements and served as control (CTR), and six other experimental diets containing different levels of BLF (800 and 1200 mg per kg diet), CHN (500 and 1000 mg per kg diet), and their combinations (400 mg BLF plus 250 mg CHN per kg diet, and 600 mg BLF plus 500 mg CHN per kg diet) for 45 days. At the end of the experiment, serum, and tissue specimens (liver and kidney) were collected, fish in all groups were challenged with A. hydrophila and then observed for another ten days to calculate the RPS. Compared to the CTR group, no significant differences were recorded in TP, ALB, GLO, BUN, and CREAT values among all treatments. Serum LYZ, ALT, AST, and ALP enzyme activities were significantly increased in all experimental groups over the CTR (P < 0.05), and their highest values were recorded in the combined treatments. Moreover, dietary supplementation with CHN (1000 mg/kg) and combined treatments significantly increased the SOD, CAT, and GSH-Px enzyme activities compared to other groups (P < 0.05). The highest mRNA expression levels of IGF-1 gene in liver, and IL-1β, and IFN-γ genes in kidneys were found in CHN (1000 mg/kg) group and combined treatments more than other groups. Interestingly, no, or mild histopathological alterations were noticed in the hepatopancreas and posterior kidney of the treated groups. A significantly higher RPS was identified in the combined treatments challenged with A. hydrophila compared with the CTR group. This study exemplifies the positive impacts of dietary supplementation with BLF or CHN alone or combinations on the antioxidative status, immunity, and disease resistance of Nile tilapia.

Topics: Aeromonas hydrophila; Animal Feed; Animals; Anti-Bacterial Agents; Antioxidants; Blood Chemical Analysis; Chitosan; Cichlids; Diet; Dietary Supplements; Disease Resistance; Dose-Response Relationship, Drug; Enzymes; Fish Diseases; Gram-Negative Bacterial Infections; Lactoferrin; Nanoparticles; Random Allocation; Transcriptome

This study investigated the effect of the dietary supplementation of bovine lactoferrin (LF) on growth performance, hematological and immunological parameters, antioxidant enzymes activity and disease resistance against Vibrio harveyi in yellowfin sea bream (Acanthopagrus latus) fingerling. The fish with initial body weight 10 ± 0.3 g were randomly distributed at 10 fish per each 250 L fiberglass tank, and fed with four experimental diets (a control basal diet and three supplemented diets with 400, 800 and 1200 mg LF kg

Topics: Adjuvants, Immunologic; Animal Feed; Animals; Antioxidants; Diet; Dietary Supplements; Disease Resistance; Dose-Response Relationship, Drug; Fish Diseases; Immunity, Innate; Lactoferrin; Random Allocation; Sea Bream; Vibrio; Vibrio Infections

Lactoferrin, a large multifunctional glycoprotein, is involved in many physiological functions but its immunomodulatory pathways are not well characterized in fish. The objective of the present study was to investigate the temporal effect of dietary bovine lactoferrin (BLf) at low (0.1%) and high (1%) on immunological organs of rainbow trout juveniles. BLf diets did not affect specific growth rate, haematocrit, splenic index, spleen respiratory burst activity as well as humoral (mIgM) and neutrophils (MPO) gene expressions after short term - 35 days (D35) and long term nutrient test - 51 days (D51) of feeding. Both low and high BLf doses induced enhanced level of plasma alternative complement activity, plasma total immunoglobulin on D35 and D51, lymphocyte plus thrombocyte cell proportion on D35 and monocyte cell proportion in total blood leukocyte cells on D51. On D51 but not on D35, BLf diets upregulated the expression of inflammatory genes in kidney for il-1 at the low BLf dose, il-8 at both BLf doses and il-6 at the high BLf dose in spleen, and il-10 at both BLf doses in kidney. Moreover, the expression of T helper (cd4-2α; cd4-2β) genes was significantly upregulated only on D51 by both BLf doses in both spleen and kidney tissues. On D51, controls and BLf treated fish were intraperitoneally injected with A. salmonicida achromogenes. The expression of 13 immune genes was evaluated at 44 h post-injection (D54). The expression of lysozyme gene was upregulated by both BLf doses after bacterial infection both in spleen and kidney. The expression of mcsfrα (spleen) and tgf-β1 (kidney) was also modulated by both BLf doses. Low and high BLf doses enhanced disease resistance of rainbow trout juveniles with the cumulative survival rate of 36% and 38% respectively while those of the control was 19% after 14 days challenged with bacteria. The results indicate that BLf diets activated the humoral immunity, associated to blood leukocyte cells of rainbow trout after short term BLf administration, and the long term BLf administration was necessary for sensitizing other lymphoid organs such as in spleen and kidney. Only after long term test, BLf diets induced significantly higher levels of innate and adaptive immune gene expressions than those of the control. Dietary BLf activated more markedly the expression of innate immune genes than the adaptive ones; this upregulation of some immune genes could explain the high disease resistance observed in rainbow trout juvenil

Topics: Administration, Oral; Aeromonas salmonicida; Animal Feed; Animals; Anti-Infective Agents; Diet; Disease Resistance; Dose-Response Relationship, Immunologic; Fish Diseases; Gene Expression; Gene Expression Profiling; Gram-Negative Bacterial Infections; Immunity, Humoral; Lactoferrin; Leukocytes; Oncorhynchus mykiss; Time Factors

The objective of this study was to identify and characterize potential biomarkers for disease resistance in bovine milk that can be used to indicate dairy cows at risk to develop future health problems. We selected high- and low-resistant cows i.e. cows that were less or more prone to develop diseases according to farmers' experience and notifications in the disease registration data. The protein composition of milk serum samples of these high- and low-resistant cows were compared using NanoLC-MS/MS. In total 78 proteins were identified and quantified of which 13 were significantly more abundant in low-resistant cows than high-resistant cows. Quantification of one of these proteins, lactoferrin (LF), by ELISA in a new and much larger set of full fat milk samples confirmed higher LF levels in low- versus high-resistant cows. These high- and low-resistant cows were selected based on comprehensive disease registration and milk recording data, and absence of disease for at least 4 weeks. Relating the experienced diseases to LF levels in milk showed that lameness was associated with higher LF levels in milk. Analysis of the prognostic value of LF showed that low-resistant cows with higher LF levels in milk had a higher risk of being culled within one year after testing than high-resistant cows. In conclusion, LF in milk are higher in low-resistant cows, are associated with lameness and may be a prognostic marker for risk of premature culling.

Topics: Animals; Biomarkers; Cattle; Cattle Diseases; Disease Resistance; Female; Lactoferrin; Lameness, Animal; Mastitis, Bovine; Milk; Prognosis; Proteomics; Tandem Mass Spectrometry

The purpose of this study was to examine sex differences in oral-respiratory mucosal immunity and the incidence, severity and duration of upper respiratory symptoms (URS) episodes in endurance athletes during a 16-week winter training period. Blood was collected from 210 subjects (147 men and 63 women) at the start and end of the study for determination of differential leukocyte counts. Timed collections of unstimulated saliva were obtained at the start and at 4-week intervals during the study period. Saliva samples were analysed for salivary antimicrobial peptides and proteins (AMPs). Weekly training and daily illness logs were kept using validated questionnaires. Training loads averaged 11 h/week of moderate-vigorous physical activity and were not different for males and females. The salivary concentration of lysozyme and lactoferrin (both P < 0.04) but not salivary immunoglobulin A (SIgA) or amylase were higher in males than females. Saliva flow rates were significantly higher in males than females (P < 0.03) and consequently so were the salivary secretion rates of lysozyme, lactoferrin and amylase (all P < 0.01) but not SIgA (P = 0.097). Total blood leukocyte, monocyte and lymphocyte counts were not different between the sexes but females had higher numbers of circulating neutrophils (P = 0.040). The average number of URS episodes was 0.6 +/- 0.8 (mean +/- SD) in males and 0.8 +/- 1.0 in females (P = 0.103) and the number of URS days was higher in females (4.7 vs 6.8 days, P < 0.02). The duration of URS episodes was longer in females (11.6 vs 15.5 days, P < 0.03). The findings of this study concur with recent reports of illness incidence at major competitive games indicating that female athletes may be more susceptible than their male counterparts to URS and that lower oral-respiratory mucosal immunity may, in part, account for this.

Topics: Amylases; Anthropometry; Athletes; Disease Resistance; Exercise; Female; Fever; Humans; Immunity, Mucosal; Immunoglobulin A, Secretory; Incidence; Lactoferrin; Leukocyte Count; Male; Medical Records; Mouth; Muramidase; Musculoskeletal Pain; Physical Endurance; Respiratory System; Respiratory Tract Diseases; Saliva; Salivary Proteins and Peptides; Secretory Rate; Sex Characteristics; Surveys and Questionnaires; Young Adult

The development of plant gene transfer systems has allowed for the introgression of alien genes into plant genomes for novel disease control strategies, thus providing a mechanism for broadening the genetic resources available to plant breeders. Using the tools of plant genetic engineering, a broad-spectrum antimicrobial gene was tested for resistance against head blight caused by Fusarium graminearum Schwabe, a devastating disease of wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) that reduces both grain yield and quality.. A construct containing a bovine lactoferrin cDNA was used to transform wheat using an Agrobacterium-mediated DNA transfer system to express this antimicrobial protein in transgenic wheat. Transformants were analyzed by Northern and Western blots to determine lactoferrin gene expression levels and were inoculated with the head blight disease fungus F. graminearum. Transgenic wheat showed a significant reduction of disease incidence caused by F. graminearum compared to control wheat plants. The level of resistance in the highly susceptible wheat cultivar Bobwhite was significantly higher in transgenic plants compared to control Bobwhite and two untransformed commercial wheat cultivars, susceptible Wheaton and tolerant ND 2710. Quantification of the expressed lactoferrin protein by ELISA in transgenic wheat indicated a positive correlation between the lactoferrin gene expression levels and the levels of disease resistance.. Introgression of the lactoferrin gene into elite commercial wheat, barley and other susceptible cereals may enhance resistance to F. graminearum.

Topics: Agrobacterium; Animals; Cattle; Disease Resistance; DNA, Complementary; Enzyme-Linked Immunosorbent Assay; Fusarium; Gene Expression Regulation, Plant; Lactoferrin; Plant Diseases; Plant Leaves; Plants, Genetically Modified; Plasmids; Transformation, Genetic; Transgenes; Triticum