Enteric defensins are essential regulators of intestinal microbial ecology

Abstract

Antimicrobial peptides are important effectors of innate immunity throughout the plant and animal kingdoms. In the mammalian small intestine, Paneth cell α-defensins are antimicrobial peptides that contribute to host defense against enteric pathogens. To determine if α-defensins also govern intestinal microbial ecology, we analyzed the intestinal microbiota in mice expressing a human α-defensin ( DEFA5) and in mice lacking an enzyme required for processing of murine α-defensins. We detected significant α-defensin-dependent changes in microbiota composition, but not in total bacterial numbers, in these complementary models. Furthermore, DEFA5-expressing mice had striking losses of Segmented Filamentous Bacteria and fewer interleukin 17-producing lamina propria T cells. These data ascribe a new homeostatic role for α-defensins in regulating the makeup of the commensal microbiota.