TY - JOUR
T1 - Heligmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity
AU - Hang, Long
AU - Setiawan, Tommy
AU - Blum, Arthur M.
AU - Urban, Joseph
AU - Stoyanoff, Korynn
AU - Arihiro, Seiji
AU - Reinecker, Hans Christian
AU - Weinstock, Joel V.
PY - 2010/9/15
Y1 - 2010/9/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1000941
DO - 10.4049/jimmunol.1000941
M3 - Article
C2 - 20702728
AN - SCOPUS:78649894385
SN - 0022-1767
VL - 185
SP - 3184
EP - 3189
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -