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Infect. Immun. doi:10.1128/IAI.00358-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

HELIGMOSOMOIDES POLYGYRUS PROMOTES REGULATORY T CELL CYTOKINE PRODUCTION IN NORMAL DISTAL MURINE INTESTINE

Division of Gastroenterology Hepatology Tufts-New England Medical Center, 750 Washington Street, Tufts-NEMC # 8387, Boston, MA 02111; Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242-1009 and the Nutrient Requirements & Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Bldg 307C Rm 213 BARC-East, Beltsville, Maryland 20705

^* To whom correspondence should be addressed. Email: david-elliott{at}uiowa.edu.

	Abstract

Helminths down-regulate inflammation and may prevent development of several autoimmune illnesses such as inflammatory bowel disease. We determined if exposure to the duodenal helminth H. polygyrus establishes cytokine pathways in the distal intestine that may protect from intestinal inflammation. Mice received 200 H. polygyrus larvae and were studied 2 wks later. Lamina propria mononuclear cells (LPMC) were isolated from the terminal ileum for analysis and in vitro experiments. Mice with H. polygyrus were resistant to trinitrobenzenesulfonic acid (TNBS)-induced colitis, a Th1 cytokine-dependent inflammation. Heligmosomoides polygyrus did not change the normal microscopic appearance of terminal ileum and colon, and minimally affected LPMC composition. However, colonization altered LPMC cytokine profiles, blocking IFN and IL12 p40 release, but promoting IL4, IL5, IL13, and IL10 secretion. IL10 blockade in-vitro with anti-IL10R mAb restored LPMC IFN and IL12 p40 secretion. IL10 blockade in vivo worsened TNBS colitis in H. polygyrus-colonized mice. LP CD4+T cells isolated from colonized mice inhibited IFN production by splenic T cells from worm-free mice. This inhibition did not require cell contact and was dependent on IL10. Heligmosomoides polygyrus-colonization inhibits Th1 and promotes Th2 and regulatory cytokine production in distant intestinal regions without changing histology or LPMC composition. IL10 is particularly important for limiting the Th1 response. The T cell origin of these cytokines demonstrates mucosal regulatory T cell induction.

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