Chapter 141 - Paneth Cell α-Defensins

Abstract

This chapter focuses on paneth cell α-defensins, which were first discovered through the genetic analyses of mouse small intestine. In the small intestine, α-defensins occur only in Paneth cells, which occupy the base of the crypts of Lieberkühn of most mammals and contain high concentrations of α-defensins in their apically directed secretory granules. Paneth cell α-defensins, having evolved to function in the extracellular environment, show broad-spectrum antimicrobial activities and constitute the majority of bactericidal peptide activity in Paneth cell secretions. The release of Paneth cell products into the crypt lumen is inferred to protect mitotically active crypt cells from colonization by potential pathogens and to confer protection from enteric infection. The most credible evidence for a Paneth cell role in enteric resistance to infection is evident from studies of mice transgenic for a human Paneth cell α-defensin, HD-5; these mice are completely immune to infection and systemic disease from orally administered Salmonella enterica serovar Typhimurium. α-Defensins in Paneth cell secretions also may interact with bacteria in the intestinal lumen above the crypt-villus boundary and influence the composition of the enteric microbial flora.