The Paneth cell and the innate immune response

Abstract

Innate immune defense of the small intestine is mediated in part by antimicrobial peptides and proteins secreted by Paneth cells, epithelial cells positioned at the base of the crypts of Lieberkuhn. Recent studies have yielded better understanding of the role that Paneth cells may play in host defense. Emerging data suggest that these cells may contribute to the pathophysiology of several human diseases. A wealth of data has also emerged on the regulatory pathways of Paneth cell functions and structure-function analysis on Paneth cell antimicrobials. This review discusses new reports in these areas. Studies of transgenic and knockout mice have supported a pivotal role of Paneth cell defensins in protection from oral bacterial pathogens. Other studies suggest that Paneth cells may be the targets of virulence mechanisms of bacterial pathogens. New observations also suggest that Paneth cell dysfunction may contribute to the clinical phenotype of Crohn disease, necrotizing enterocolitis, and, perhaps, intestinal manifestations of cystic fibrosis. Paneth cells are emerging as key mediators of innate host defense in the small intestine. The antimicrobial activity of Paneth cell secretory products on transient and resident microbes in the gut may have a profound influence on health. The possible role of Paneth cell dysfunction in human disease and a better understanding of Paneth cell regulatory pathways are areas poised for significant advances in the near future.