title: Transmembrane tumor necrosis factor alpha is required for enteropathy and is sufficient to promote parasite expulsion in gastrointestinal helminth infection.
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-alpha/lymphotoxin alpha (LTalpha)(-/-) mice expressing noncleavable transgenic tmTNF to those of TNF-alpha/LTalpha(-/-) and wild-type mice. The susceptibility of TNF-alpha/LTalpha(-/-) 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/LTalpha(-/-) 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/LTalpha(-/-) 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.
authors: SIPBS, University of Strathclyde, Glasgow G4 0NR, United Kingdom.
authors: M X
authors: MX
authors: Ierna
authors: H E
authors: HE
authors: Scales
authors: C
authors: C
authors: Mueller
authors: C E
authors: CE
authors: Lawrence
mesh_terms: D000818:Animals; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D020382:Interleukin-18 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018418:Th2 Cells / Q000276:immunology; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D020382:Interleukin-18; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E