The cytokine TGFβ is crucial in regulating immunity in the intestine, but its role and regulation during responses to intestinal infection is not well understood. We therefore addressed how TGFβ functions and is controlled during chronic intestinal infection, using the model murine parasite Trichuris muris (the human homologue of which affects ~600 million people world-wide, causing severe health problems). We found that TGFβ signalling is induced early during infection, specifically in CD4+ T-cells. This enhanced signalling involves expression of the TGFβ-activating integrin αvβ8 by dendritic cells (DCs). Importantly, mice lacking integrin αvβ8 on DCs are completely resistant to chronic infection with T. muris, indicating an important functional role for integrin αvβ8-mediated TGFβ activation in promoting chronic infection. Protection from infection is dependent on CD4+ T-cells, but is independent of Foxp3+ Tregs as mice depleted of Foxp3+ Tregs during infection remained susceptible to infection. Instead, lack of integrin αvβ8 on DCs led to an early increase in expression of the Th2 cytokine IL-13 by CD4+ T-cells which is required for protection from infection. Our results therefore provide novel insights into how type 2 immunity is controlled in the intestine during gastrointestinal parasite infection, and may help contribute to the development of new therapies aimed at promoting expulsion of gut parasites.
- Copyright © 2013 by The American Association of Immunologists, Inc.