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PMID: 12796512 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mast cells disrupt epithelial barrier function during enteric nematode infection.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 13 ·2003-06-24 ·Pages 7761-6

McDermott JR, Bartram RE, Knight PA, Miller HR, Garrod DR, Grencis RK

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.

MeSH Terms
Animals Blotting, Western Chemokine CCL2/genetics Epithelial Cells/parasitology Epithelium/metabolism,parasitology,physiology Immunoglobulin G/metabolism Inflammation Interleukin-9/genetics Intestines/parasitology Jejunum/parasitology Mast Cells/metabolism Membrane Proteins/metabolism Mice Mice, Inbred BALB C Mice, Transgenic Mucous Membrane/metabolism Occludin Proto-Oncogene Proteins c-kit/immunology Time Factors Trichinella spiralis/pathogenicity
Chemicals
Chemokine CCL2 Immunoglobulin G Interleukin-9 Membrane Proteins Occludin Ocln protein, mouse Proto-Oncogene Proteins c-kit
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
McDermott Jacqueline R
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom. jacqueline.r.mcdermott@man.ac.uk
Bartram Ruth E
Knight Pamela A
Miller Hugh R P
Garrod David R
Grencis Richard K
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1231488100
Email
jacqueline.r.mcdermott@man.ac.uk
Published
2003-06-24
Epub
2003-00-09
Pages
7761-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC164661
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.1231488100 PMC Full Text View journal details
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