Transmembrane tumor necrosis factor alpha is required for enteropathy and is sufficient to promote parasite expulsion in gastrointestinal helminth infection

M.X. Ierna, H.E. Scales, C. Mueller, C.E. Lawrence

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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-α/lymphotoxin alpha (LTα)−/− mice expressing noncleavable transgenic tmTNF to those of TNF-α/LTα−/− and wild-type mice. The susceptibility of TNF-α/LTα−/− 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-α/LTα−/− 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-α/LTα−/− 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-α is required for the induction of Th2 immune responses related to infection with gastrointestinal helminth parasites.
Original languageEnglish
Pages (from-to)3879-3885
Number of pages7
JournalInfection and Immunity
Volume77
Issue number9
DOIs
Publication statusPublished - Sep 2009

Keywords

  • transmembrane tumor
  • necrosis factor alpha
  • enteropathy
  • parasite expulsion
  • gastrointestinal helminth infection

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