Heligmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity

Long Hang, Tommy Setiawan, Arthur M. Blum, Joseph Urban, Korynn Stoyanoff, Seiji Arihiro, Hans Christian Reinecker, Joel V. Weinstock

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Less developed countries have a low incidence of immunological diseases like inflammatory bowel disease (IBD), perhaps prevented by the high prevalence of helminth infections in their populations. In the Rag IL-10-/- T cell transfer model of colitis, Heligmosomoides polygyrus, an intestinal helminth, prevents and reverses intestinal inflammation. This model of colitis was used to explore the importance of innate immunity in H. polygyrus protection from IBD. Rag mice briefly exposed to H. polygyrus before reconstitution with IL-10-/- colitogenic T cells are protected from colitis. Exposure to H. polygyrus before introduction of IL-10-/- and OT2 T cells reduced the capacity of the intestinal mucosa to make IFN-γ and IL-17 after either anti-CD3 mAb or OVA stimulation. This depressed cytokine response was evident even in the absence of colitis, suggesting that the downmodulation in proinflammatory cytokine secretion was not just secondary to improvement in intestinal inflammation. Following H. polygyrus infection, dendritic cells (DCs) from the lamina propria of Rag mice displayed decreased expression of CD80 and CD86, and heightened expression of plasmacytoid dendritic cell Ag-1 and CD40. They were also less responsive to lamina proprias, producing less IL-12p40 and IL-10. Also diminished was their capacity to present OVA to OT2 T cells. These experiments infer that H. polygyrus does not require direct interactions with Tor B cells to render animals resistant to colitis. DCs have an important role in driving both murine and human IBD. Data suggest that phenotypic alternations in mucosal DC function are part of the regulatory process.

Original languageEnglish (US)
Pages (from-to)3184-3189
Number of pages6
JournalJournal of Immunology
Volume185
Issue number6
DOIs
StatePublished - Sep 15 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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