Defensins and mucosal protection

Abstract

The gastrointestinal tract is constantly exposed to microorganisms, mainly a large and complex population of bacteria resident in the colon and distal small intestine. Although the normal host relationship with the resident luminal bacteria is often mutually beneficial, the host also requires protection against these microorganisms. Epithelial cells play a critical role in mediating these protective responses and there is increasing appreciation of the likely importance of antimicrobial peptides of the defensin family that they express. The enteric alpha-defensins (human defensins [HD]5 and 6) are expressed by Paneth cells, which are normally confined to the small intestine, but are also seen in the colon in patients with inflammatory bowel disease. Studies have shown that HD5 is stored in Paneth cell granules in precursor form and requires processing to the mature peptide. Human beta-defensin (HBD)1 is constitutively expressed in intestinal epithelial cells, whereas the expression of HBD2 is induced in inflammatory bowel disease. HBDs have also been shown to be chemotactic for immature dendritic cells and memory T cells. Thus, they may not only mediate innate immunity, but also regulate adaptive immune responses in inflammatory bowel disease.