Innate immune defenses in the intestinal tract

Innate intestinal defenses are important for protection against ingested and commensal microbes. This review highlights recent new insights into innate immune effectors in the intestine.

Intestinal epithelial cells, particularly Paneth cells, are the major producers of multiple peptides and proteins with antimicrobial activity in the intestine. The most abundant and diverse of these are the defensins. They are highly microbicidal in vitro and probably important in vivo, yet their physiologic functions remain incompletely understood. Relative defensin deficiency may be a risk factor for Crohn's disease and infectious diarrhea. Cathelicidin contributes to mucosal defense against epithelial-adherent bacterial pathogens, and helps to set a threshold for productive infection. Bactericidal/permeability-inducing protein has lipopolysaccharide-neutralizing capacity and kills bacteria when overexpressed in epithelial cells. Resistin-like molecule beta is important in mucosal defense against helminths due to its ability to inhibit worm chemotaxis. Antimicrobial lectins, particularly hepatocarcinoma-intestine-pancreas/pancreatic-associated protein, RegIII, and intelectin, can lyse bacteria or interfere with their attachment to epithelial cells.

Discovery of an expanding set of antimicrobial effectors supports the evolutionary importance of innate intestinal defenses against microbial threats, but also underlines the physiologic and pharmacologic need for a better understanding of the respective functions of these molecules.