Bovine colostrum enhances natural killer cell activity and immune response in a mouse model of influenza infection and mediates intestinal immunity through toll-like receptors 2 and 4

• Published in: Nutrition research (New York, N.Y.) Vol. 34; no. 4; pp. 318 - 325
• Main Authors: Wong, Eric B, Mallet, Jean-François, Duarte, Jairo, Matar, Chantal, Ritz, Barry W
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-04-2014; Elsevier
• Subjects: Animals; Antibodies - metabolism; Biological and medical sciences; Biological Products - pharmacology; Biological Products - therapeutic use; C57BL/6 mice; Cattle; Colostrum; Colostrum - immunology; Disease Models, Animal; Epithelial Cells - drug effects; Epithelial Cells - immunology; Epithelial Cells - metabolism; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Human viral diseases; Humans; Immunity - drug effects; Infection; Infectious diseases; Influenza A virus; Influenza A Virus, H1N1 Subtype; Influenza, Human - immunology; Influenza, Human - metabolism; Influenza, Human - virology; Interleukin-6 - metabolism; Intestinal Mucosa - drug effects; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestine, Small - drug effects; Intestine, Small - immunology; Intestine, Small - metabolism; Killer Cells, Natural - metabolism; Lung - drug effects; Lung - virology; Medical sciences; Mice, Inbred BALB C; Natural killer cells; Orthomyxoviridae Infections - drug therapy; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - metabolism; Orthomyxoviridae Infections - virology; Pregnancy; Spleen - cytology; Spleen - drug effects; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Weight Loss - drug effects; CPM; IgA; IgG; ATCC; LPS; Hank's balanced salt solution; interleukin 6; natural killer; American Type Culture Collection; TLR; Natural killer cells; counts per minute; immunoglobulin G; 50% tissue culture infectious dose; IEC; immunoglobulin A; hemagglutinating units; IL-6; Infection; intestinal epithelial cell; Influenza A virus; TCID 50; C57BL/6 mice; toll-like receptor; HBSS; Colostrum; lipopolysaccharide; HAU; NK; TCID50; Animal model; Ox; Toll like receptor; Immunity; Influenza A; Ungulata; Immune response; Bovine; Nutrition; Digestive system; Rodentia; Gut; Natural killer cell; Virus; Vertebrata; Mammalia; Mouse; Viral disease; Animal; Artiodactyla; C57BU6 mice
• ISSN: 0271-5317; 1879-0739
• DOI: 10.1016/j.nutres.2014.02.007

Abstract Oral administration of bovine colostrum affects intestinal immunity, including an increased percentage of natural killer (NK) cells. However, effects on NK cell cytotoxic activity and resistance to infection as well as a potential mechanism remain unclear. Therefore, we investigated the effects of bovine colostrum (La Belle, Inc, Bellingham, WA) on the NK cytotoxic response to influenza infection and on toll-like receptor (TLR) activity in a primary intestinal epithelial cell culture. We hypothesized that colostrum would increase NK cell activity and that TLR-2 and TLR-4 blocking would reduce interleukin 6 production by epithelial cells in response to contact stimulation with colostrum. Four-month-old female C57BL/6 mice were supplemented with 1 g of colostrum per kilogram of body weight before and after infection with influenza A virus (H1N1). Animals were assessed for weight loss, splenic NK cell activity, and lung virus titers. Colostrum-supplemented mice demonstrated less reduction in body weight after influenza infection, indicating a less severe infection, increased NK cell cytotoxicity, and less virus burden in the lungs compared with controls. Colostrum supplementation enhanced NK cell cytotoxicity and improved the immune response to primary influenza virus infection in mice. To investigate a potential mechanism, a primary culture of small intestine epithelial cells was then stimulated with colostrum. Direct activation of epithelial cells resulted in increased interleukin 6 production, which was inhibited with TLR-2 and TLR-4 blocking antibodies. The interaction between colostrum and immunity may be dependent, in part, on the interaction of colostrum components with innate receptors at the intestinal epithelium, including TLR-2 and TLR-4.