Defensins and Innate Immunity of the Mammalian Small Intestine

The release of gene-encoded antimicrobial peptides by epithelial cells is thought to contribute to innate mucosal immunity. Defensins are a predominant class of such antimicrobial peptides in mammals. These cysteine-rich cationic peptides have antibiotic activity against a wide range of bacteria and other microbes. In the mammalian small intestine, Paneth cells at the base of the crypts of Lieberkühn secrete defensins and other antibiotic proteins. These Paneth cell antimicrobials are proposed to have several overlapping functions. First, they likely help to protect the epithelial stem cells from noxious microbes. The stem cells, which reside at the neck of the crypt, are responsible for continual renewal of cells necessary for maintained integrity of the surface epithelium lining the villi and crypts. Second, defensins and other Paneth cell products likely interact with bacteria that exist in the intestinal lumen. Based on relative sensitivity to these antimicrobials, the composition of the enteric microbial flora might be influenced. Third, enteric defensins may regulate the numbers of colonising microbes in the small intestine. Forth, enteric defensins may contribute to defence from food and water borne pathogens in the intestinal lumen. Further defining the contributions of Paneth cell defensins to innate defence should improve our understanding of normal small bowel function. Given that microbial products stimulate Paneth cell secretion, it is possible that the mechanism of action of probiotic agents may, in part, involve modulating Paneth cell secretion.