Heligmosomoides polygyrus abrogates antigen-specific gut injury in a murine model of inflammatory bowel disease

Developing countries have a low incidence of inflammatory bowel disease (IBD), perhaps prevented by the high prevalence of helminth infections and other alterations in intestinal flora and fauna. Helminth infections prevent colitis in various murine models of IBD. IBD may be driven by an aberrant immune response to luminal antigen(s).

We developed a murine IBD model featuring antigen-specific enterocolitis and demonstrate for the first time that gut inflammation induced by an antigen could be abrogated by H. polygyrus infection. Protection was associated with suppressed IL-17 and IFN-γ production, induction of Foxp3(+) Tregs, and elevated secretion of non-T-cell-derived IL-10, all of which could be part of the protective processes.

We developed a murine model of IBD in which gut injury was induced by a specific antigen to better simulate the IBD disease process and to determine if helminth infections could abolish gut injury induced by an orally administered antigen. The model features pan-enterocolitis triggered by feeding ovalbumin (OVA).

The intestinal inflammation is antigen-specific and generates interleukin (IL)-17 and interferon-gamma (IFN-γ), but not IL-4. Full expression of the disease required T cells with defective capacity to make IL-10 and treatment with a noninjurious, low dose of a nonsteroidal antiinflammatory drug. Exposure to Heligmosomoides polygyrus abrogated this antigen-induced gut injury. H. polygyrus colonization induced Foxp3(+) T regulatory cells (Tregs) and mucosal production of IL-10 from non-T cells. Lamina propria mononuclear cells from H. polygyrus-infected mice released less IL-17 and IFN-γ constitutively and when stimulated with OVA or anti-CD3/CD28 monoclonal antibodies. Conclusions: We developed a murine IBD model featuring antigen-specific enterocolitis and demonstrate for the first time that gut inflammation induced by an antigen could be abrogated by H. polygyrus infection. Protection was associated with suppressed IL-17 and IFN-γ production, induction of Foxp3(+) Tregs, and elevated secretion of non-T-cell-derived IL-10, all of which could be part of the protective processes.