Mast Cells Disrupt Epithelial Barrier Function During Enteric Nematode Infection

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Jun 11

PMID 12796512

Citations 126

Authors

Jacqueline R McDermott

Ruth E Bartram

Pamela A Knight

Hugh R P Miller

David R Garrod

Richard K Grencis

Affiliations

Soon will be listed here.

Abstract

We have investigated the influence of mast cells on the barrier function of intestinal epithelium during nematode infection. Trichinella spiralis infection induces a strong type 2 cytokine-mediated inflammation, resulting in a critical mucosal mastocytosis that is known to mediate expulsion of the parasites from the intestine. The host response to infection is also characterized by an increase in mucosal leakiness. We show here that intestinal epithelial permeability is markedly elevated during infection, with kinetics that mirror the adaptive immune response to primary and secondary infection. Furthermore, we have identified degradation of the tight junction protein, occludin, thereby providing a mechanism for increased paracellular permeability during helminth infection. We further demonstrate by using anti-c-kit antibody and IL-9 transgenic mice that mast cells are directly responsible for increasing epithelial paracellular permeability and that mice deficient in a mast cell-specific protease fail to increase intestinal permeability and fail to expel their parasite burden. These results provide the mechanism whereby mucosal mast cells mediate parasite expulsion from the intestine.

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