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.
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.
Department of Biology, Drexel University, Philadelphia, PA 19104.
Eric B
EB
Wong
Department of Nutrition, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada, K1N 7K4.
Jean-François
JF
Mallet
Department of Nutrition, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada, K1N 7K4.
Jairo
J
Duarte
Department of Nutrition, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada, K1N 7K4.
Chantal
C
Matar
Department of Biology, Drexel University, Philadelphia, PA 19104; Nutrition Sciences Department, College of Nursing and Health Professions, Drexel University, Philadelphia, PA 19102. Electronic address: br@atrium-innovations.com.
Barry W
BW
Ritz
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use; D002417:Cattle; D003126:Colostrum / Q000276:immunology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007109:Immunity / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000821:virology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D011247:Pregnancy; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015431:Weight Loss / Q000187:drug effects
D000906:Antibodies; D001688:Biological Products; D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
C57BL/6 mice; Colostrum; Infection; Influenza A virus; Natural killer cells