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Colonization with Heligmosomoides polygyrus Suppresses Mucosal IL-17 Production¹

David E. Elliott^2,*,, Ahmed Metwali^*,, John Leung^*,, Tommy Setiawan, Arthur M. Blum, M. Nedim Ince^*,, Lindsey E. Bazzone, Miguel J. Stadecker, Joseph F. Urban, Jr.^¶ and Joel V. Weinstock^*

^* Department of Veterans Affairs Medical Center, Iowa City, IA 52246; Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242; Division of Gastroenterology-Hepatology, Tufts-New England Medical Center, Boston, MA 02111; Department of Pathology, Tufts University School of Medicine, Boston, MA 02111; and ^¶ Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705

Helminth exposure appears to protect hosts from inappropriate inflammatory responses, such as those causing inflammatory bowel disease. A recently identified, strongly proinflammatory limb of the immune response is characterized by T cell IL-17 production. Many autoimmune type inflammatory diseases are associated with IL-17 release. Because helminths protect from these diseases, we examined IL-17 production in helminth-colonized mice. We colonized mice with Heligmosomoides polygyrus, an intestinal helminth, and analyzed IL-17 production by lamina propria mononuclear cells (LPMC) and mesenteric lymph node (MLN) cells. Colonization with H. polygyrus reduces IL-17A mRNA by MLN cells and inhibits IL-17 production by cultured LPMC and MLN cells. Helminth exposure augments IL-4 and IL-10 production. Blocking both IL-4 and IL-10, but not IL-10 alone, restores IL-17 production in vitro. Colonization of colitic IL-10-deficient mice with H. polygyrus suppresses LPMC IL-17 production and improves colitis. Ab-mediated blockade of IL-17 improves colitis in IL-10-deficient mice. Thus, helminth-associated inhibition of IL-17 production is most likely an important mechanism mediating protection from inappropriate intestinal inflammation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the National Institutes of Health (DK38327, DK58755, AI49382, DK07663, DK25295, DK034928, and AI018919), the Department of Veterans Affairs Office of Research and Development, and the Crohn’s and Colitis Foundation of America.

² Address correspondence and reprint requests to Dr. David E. Elliott, Division of Gastroenterology (4611 JCP), University of Iowa Hospital and Clinics, 200 Hawkins Drive, Iowa City, IA 52242-1009. E-mail address: david-elliott{at}uiowa.edu

³ Abbreviations used in this paper: IBD, inflammatory bowel disease; EAE, experimental autoimmune encephalitis; LPMC, lamina propria mononuclear cell; MLN, mesenteric lymph node; MS, multiple sclerosis; TNBS, trinitrobenzenesulfonic acid.