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Infection with a Helminth Parasite Prevents Experimental Colitis via a Macrophage-Mediated Mechanism¹

Philip Smith^*, Niamh E. Mangan^*, Caitriona M. Walsh^*, Rosie E. Fallon^*, Andrew N. J. McKenzie, Nico van Rooijen and Padraic G. Fallon^2,*

^* Institute of Molecular Medicine, St. James’s Hospital, Trinity College Dublin, Dublin, Ireland; Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom; and Vrije Univeriteit, Amsterdam, The Netherlands

The propensity of a range of parasitic helminths to stimulate a Th2 or regulatory cell-biased response has been proposed to reduce the severity of experimental inflammatory bowel disease. We examined whether infection with Schistosoma mansoni, a trematode parasite, altered the susceptibility of mice to colitis induced by dextran sodium sulfate (DSS). Mice infected with schistosome worms were refractory to DSS-induced colitis. Egg-laying schistosome infections or injection of eggs did not render mice resistant to colitis induced by DSS. Schistosome worm infections prevent colitis by a novel mechanism dependent on macrophages, and not by simple modulation of Th2 responses, or via induction of regulatory CD4⁺ or CD25⁺ cells, IL-10, or TGF-. Infected mice had marked infiltration of macrophages (F4/80⁺CD11b⁺CD11c^–) into the colon lamina propria and protection from DSS-induced colitis was shown to be macrophage dependent. Resistance from colitis was not due to alternatively activated macrophages. Transfer of colon lamina propria F4/80⁺ macrophages isolated from worm-infected mice induced significant protection from colitis in recipient mice treated with DSS. Therefore, we propose a new mechanism whereby a parasitic worm suppresses DSS-induced colitis via a novel colon-infiltrating macrophage population.

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 Wellcome Trust, Science Foundation Ireland, and the Higher Education Authority Programme for Research in Third Level Institutions.

² Address correspondence and reprint requests to Dr. Padraic G. Fallon, Institute of Molecular Medicine, St. James’s Hospital, Trinity College Dublin, Dublin 8, Ireland. E-mail address: pfallon{at}tcd.ie

³ Abbreviations used in this paper: IBD, inflammatory bowel disease; CD, Crohn’s disease; UC, ulcerative colitis; DSS, dextran sodium sulfate; DAI, disease activity index; eGFP, enhanced GFP; LP, lamina propria; iNOS, inducible NO synthase; nor-NOHA, N-hydroxy-nor-L-of arginine.

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