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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Diet, Genomics and Immunology Laboratory » Research » Publications at this Location » Publication #282738
Title: Heligmosomoides polygyrus bakeri infection activates colonic FoxP3+ T cells enhancing their capacity to prevent colitis

Author
item HANG, LONG - Tufts - New England Medical Center
item BLUM, ARTHUR - Tufts - New England Medical Center
item SETIAWAN, TOMMY - Tufts - New England Medical Center
item Urban, Joseph
item STOYANOFF, KORYNN - Tufts - New England Medical Center
item WEINSTOCK, JOEL - Tufts - New England Medical Center

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/12/2013
Publication Date: 8/15/2013
Citation: Hang, L., Blum, A.M., Setiawan, T., Urban Jr, J.F., Stoyanoff, K., Weinstock, J.V. 2013. Heligmosomoides polygyrus bakeri infection activates colonic FoxP3+ T cells enhancing their capacity to prevent colitis. Journal of Immunology. 191(4):1927-34.

Interpretive Summary: Helminth (worm) parasites can immune modulate local inflammation at mucosal surfaces including the intestine. This phenomenon has been used for a therapeutic application of parasitic whipworm eggs in humans expressing inflammatory bowel disease (IBD). The mechanism of action of this treatment is largely speculative, but it is clear that regulatory cells and cell products contribute to this response. Mice can be used to experimentally test and acquire information on worm-induced regulatory networks to help design strategies to effectively eliminate harmful worm infections or utilize their anti-inflammatory properties to modulate disease in livestock and humans. This study used an experimental model of inflammatory bowel disease (IBD) to induce inflammation in the intestine and studied the role that worm infection played in modulating the response. It was observed that the worm induced a population of regulatory T cells (Tregs) in the intestine that could transfer the modulating effects to naïve hosts and prevent the onset of IBD. A specific subset of Tregs was needed to migrate to the mucosal layer of the intestine after transfer into the mouse and reverse immune-based colitis. These results provide a target host cell responsible for the modulating effects of the worm and should generate strategies to regulate the activity of Tregs, including changes in diet that could modulate inflammation at mucosal surfaces. The information is important to researchers that study the control of infectious diseases in humans and livestock, and the relationship between parasitic infection and inflammation.

Technical Abstract: Helminthic infections protect mice from colitis in murine models of inflammatory bowel disease and also may protect people. Helminths like Heligmosomoides bakeri (Hpb) can induce Tregs. Experiments explored if Hpb infection could protect mice from colitis through activation of colonic Treg and examined mechanisms of action. We showed that Hpb infection increased the number of T cells expressing Foxp3 in the colon. More importantly, Foxp3+/IL10- and Foxp3+/IL10+ T cell subsets isolated from the colon of Hpb infected mice prevented colitis when adoptively transferred into a murine model of IBD, while Tregs from uninfected mice could not provide protection. Only the transferred colonic Foxp3+/IL10- T cells from Hpb infected animals readily accumulated in the colon and MLN of recipient animals, and they reconstituted both the Foxp3+/IL10- and Foxp3+/IL10+ T cell subsets. However, transferred Foxp3+/IL10+ T cells disappeared. IL10 expression by Foxp3+ T cells was necessary for colitis prevention. Thus, Hpb infection activates colonic Foxp3+ T cells making them highly regulatory. The Foxp3+ T cells that fail to express IL10 may be critical for populating the colon with the Foxp3+/IL10+ T cells, which are required to control colitis.