Springer Seminars in Immunopathology

, Volume 27, Issue 2, pp 133–146

Paneth cell α-defensins: peptide mediators of innate immunity in the small intestine

Original Paper

DOI: 10.1007/s00281-005-0202-x

Cite this article as:
Ouellette, A.J. Springer Semin Immun (2005) 27: 133. doi:10.1007/s00281-005-0202-x

Abstract

Epithelial cells contribute to innate immunity by releasing antimicrobial peptides (AMPs) onto mucosal surfaces. In the small bowel, Paneth cells at the base of the crypts of Lieberkühn secrete α-defensins and additional AMPs at high levels in response to cholinergic stimulation and when exposed to bacterial antigens. The release of Paneth cell products into the crypt lumen is inferred to protect mitotically active crypt cells that renew the epithelial cell monolayer from colonization by potentially pathogenic microbes and to confer protection from enteric infection. The most compelling 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, which are completely immune to infection and systemic disease from orally administered Salmonella enterica serovar typhimurium. Cystic fibrosis mice are subject to small bowel bacterial overgrowth that is associated with impaired dissolution of released Paneth cell granules in the crypt lumen. Mutations that cause defects in the activation, secretion, dissolution, and bactericidal effects of Paneth cell AMPs may alter crypt innate immunity and contribute to immunopathology.

Keywords

Antimicrobial peptideExocytosisEpitheliumDense granulesMucosal immunity

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Departments of Pathology and Laboratory Medicine and Microbiology and Molecular Genetics, School of Medicine, College of Health SciencesUniversity of California at IrvineIrvineUSA