Mouse mast cell protease-1 is required for the enteropathy induced by gastrointestinal helminth infection in the mouse.
OBJECTIVE
The relationship between intestinal pathology and immune expulsion of gastrointestinal nematodes remains controversial. Immune expulsion of gastrointestinal helminth parasites is usually associated with Th2 responses, but the effector mechanisms directly responsible for parasite loss have not been elucidated. Mast cell hyperplasia is a hallmark of infection with gastrointestinal nematodes, in particular Trichinella spiralis. Although the precise mechanism by which mast cells induce expulsion of these parasites has not been elucidated, it has been proposed that mast cell mediators, including cytokines and granule chymases, act to create an environment inhospitable to the parasite, part of this being the induction of intestinal inflammation. Therefore, the aims of this study were to dissect the role of mast cells and mast cell proteases in the induction of parasite-induced enteropathy.


METHODS
Mast cell-deficient W/Wv and mouse mast cell protease-1 (mMCP-1)-deficient mice were infected with T. spiralis, and parasite expulsion, enteropathy, and Th2 responses were determined.


RESULTS
Expulsion of the parasite was delayed in both strains of mice compared with wild-type controls; additionally, in both cases, the enteropathy was significantly ameliorated. Although Th2 responses were significantly reduced in mast cell-deficient W/Wv mice, those from mMCP-1-deficient mice were similar to wild-type mice. Additionally, levels of TNF-alpha and nitric oxide were significantly reduced in both W/Wv and mMCP-1 deficient mice.


CONCLUSIONS
These results imply that mast cells may contribute to the induction of protective Th2 responses and, importantly, that the intestinal inflammation associated with gastrointestinal helminths is partly mediated by mMCP-1.
Lawrence
Catherine E
CE
Department of Immunology, SIBS, Strathclyde University, Glasgow, United Kingdom. catherine.lawrence@strath
Paterson
Yvonne Y W
YY
Wright
Steven H
SH
Knight
Pamela A
PA
Miller
Hugh R P
HR
D000818:Animals; D053818:Chymases; D006790:Host-Parasite Interactions / Q000276:immunology; D007411:Intestinal Diseases, Parasitic / Q000209:etiology / Q000276:immunology*; D051379:Mice; D012697:Serine Endopeptidases / Q000009:adverse effects / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D017160:Trichinella spiralis / Q000276:immunology*; D014235:Trichinellosis / Q000150:complications / Q000276:immunology*
D012697:Serine Endopeptidases; D053818:Chymases; C509230:Mcpt1 protein, mouse