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

Ierna, M.X., Scales, H.E. , Mueller, C. and Lawrence, C.E. (2009) Transmembrane tumor necrosis factor alpha is required for enteropathy and is sufficient to promote parasite expulsion in gastrointestinal helminth infection. Infection and Immunity, 77(9), pp. 3879-3885. (doi: 10.1128/IAI.01461-08) (PMID:19564380) (PMCID:PMC2737992)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Scales, Dr Hannah
• Authors: Ierna, M.X., Scales, H.E., Mueller, C., and Lawrence, C.E.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Infection and Immunity
• Publisher: American Society for Microbiology
• ISSN: 0019-9567
• ISSN (Online): 1098-5522
• Published Online: 29 June 2009