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Infection and Immunity, September 2009, p. 3879-3885, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.01461-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Transmembrane Tumor Necrosis Factor Alpha Is Required for Enteropathy and Is Sufficient To Promote Parasite Expulsion in Gastrointestinal Helminth Infection{triangledown}

M. X. Ierna,1 H. E. Scales,1 C. Mueller,2 and C. E. Lawrence1*

SIPBS, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom,1 Institute of Pathology, Division of Experimental Pathology, University of Bern, CH-3010 Bern, Switzerland2

Received 1 December 2008/ Returned for modification 1 January 2009/ Accepted 22 June 2009

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-{alpha}/lymphotoxin alpha (LT{alpha})–/– mice expressing noncleavable transgenic tmTNF to those of TNF-{alpha}/LT{alpha}–/– and wild-type mice. The susceptibility of TNF-{alpha}/LT{alpha}–/– mice to T. spiralis infection was associated with impaired induction of a protective Th2 response and the lack of mucosal mastocytosis. Although tmTNF-expressing transgenic (tmTNF-tg) mice also had a reduced Th2 response, the mast cell response was greater than that observed in TNF-{alpha}/LT{alpha}–/– 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 the infection of wild-type mice, while pathology in TNF-{alpha}/LT{alpha}–/– mice 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-{alpha} is required for the induction of Th2 immune responses related to infection with gastrointestinal helminth parasites.

* Corresponding author. Mailing address: SIPBS, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom. Phone: 0141 548 2104. Fax: 0141 552 2562. E-mail: catherine.lawrence{at}strath.ac.uk

{triangledown} Published ahead of print on 29 June 2009.

Editor: J. F. Urban, Jr.

Infection and Immunity, September 2009, p. 3879-3885, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.01461-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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