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Nitric oxide mediates intestinal pathology but not immune expulsion during Trichinella spiralis infection in mice

Lawrence, Catherine E., Paterson, Jacqueline C. M., Wei, Xiao-Qing, Liew, Foo Y., Garside, Paul and Kennedy, Malcolm W. 2000. Nitric oxide mediates intestinal pathology but not immune expulsion during Trichinella spiralis infection in mice. The Journal of Immunology 164 (8) , pp. 4229-4234.

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The relationship between intestinal pathology and immune expulsion of gastrointestinal (GI) nematodes remains controversial. Although immune expulsion of GI helminth parasites is usually associated with Th2 responses, the effector mechanisms directly responsible for parasite loss have not been identified. We have previously shown that while the intestinal pathology accompanying the expulsion of the GI parasite Trichinella spiralis may be dependent on IL-4 and mediated by TNF, parasite loss is independent of TNF. In contrast, intestinal pathology in other disease models has been attributed to Th1 cytokines, although it closely resembles that seen in helminth infections. Whereas production of inducible NO synthase (iNOS) in the gut is important for both homeostasis of the epithelial layer and in protection against pathogenic microorganisms, overproduction of NO has been implicated in the pathogenesis of a number of inflammatory conditions. We therefore investigated the role of NO in T. spiralis infection using iNOS-deficient mice. iNOS−/− and iNOS-/+ mice were infected with T. spiralis, and parasite expulsion and intestinal pathology were followed. Parasite expulsion proceeded similarly in both groups of animals, but significant intestinal pathology was only observed in the heterozygous mice. Thus it appears that, although the protective effects of Th2 responses in GI helminth infection do not require NO, this mediator contributes substantially to the associated enteropathy. NO may therefore be an important mediator of enteropathy in both Th1- and Th2-inducing conditions.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 04 Jun 2017 04:16

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