IAI Accepts, published online ahead of print on 29 June 2009

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ierna, M. X. Articles by Lawrence, C. E. Search for Related Content PubMed PubMed Citation Articles by Ierna, M. X. Articles by Lawrence, C. E.

 Previous Article  |  Next Article 

Infect. Immun. doi:10.1128/IAI.01461-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Transmembrane TNF- is required for enteropathy and is sufficient to promote parasite expulsion in gastrointestinal helminth infection

M. X. Ierna, H. E. Scales, C. Mueller, and C. E. Lawrence^*

SIPBS, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR; Institute of Pathology, Division of Experimental Pathology, University of Bern, CH-3010, Bern, Switzerland

^* To whom correspondence should be addressed. Email: catherine.lawrence{at}strath.ac.uk.

To study the specific role of transmembrane tumor necrosis factor (tmTNF) in protective and pathological responses against the gastrointestinal helminth Trichinella spiralis, we compared the immune responses of TNF- /lymphotoxin (LT)- ^-/- mice expressing a noncleavable transgenic tmTNF (tmTNFtg) to those of TNF-/LT-/- and wild-type mice. Susceptibility of TNF-/LT-/- mice to T. spiralis infection was associated with impaired induction of a protective Th2 response and lack of a mucosal mastocytosis. Although tmTNFtg mice also had a reduced Th2 response, the mast cell response was greater than that observed in TNF-/LT-/- mice and was sufficient to induce the expulsion of the parasite. T. spiralis infection of tmTNF-tg mice resulted in significant intestinal pathology characterized by villus atrophy and crypt hyperplasia comparable to that induced following infection of wild type mice while pathology in TNF-/LT-/- was significantly reduced. Our data thus indicate a role for tmTNF in host defense against gastrointestinal helminths and in the accompanying enteropathy. Furthermore, they also demonstrate that TNF- is required for the induction of Th2 immune responses associated with infection by gastrointestinal helminth parasites.