A central role for Type I IFN in the induction of Th2 responses by dendritic cells

Abstract

Abstract Although dendritic cells (DCs) are critical for induction of Th2 immunity against helminths or allergens, relatively little is known about how they become activated and function in response to Th2-polarizing antigens. We have discovered a previously unrecognized role for Type I IFN (IFN-I) in the optimal activation and function of DCs following exposure to strongly Th2-polarizing antigens. To date, IFN-I has primarily been associated with anti-viral immunity, and its role in Th2 settings is currently unclear. DCs exposed to total egg antigens from the parasitic helminth Schistosoma mansoni, or the primary immunostimulatory component of S. mansoni eggs, omega-1, produced IFN-I in vitro. IFN-I was also detected in response to the common allergen house dust mite (HDM). DCs lacking the IFN-I receptor displayed a dramatically impaired ability to induce Th2 cytokines in vivo, but unimpaired ability to support CD4 T cell polarization in vitro. Further, Th2-promoting DCs depended on IFN-I signaling for optimal activation, efficient migration to the draining LN, and effective localization within the T cell zone. In vivo challenge of naïve mice with S. mansoni eggs or HDM in the absence of the IFN-I receptor induced significantly reduced levels of Th2 cytokines compared to controls. Together, our data suggest a key role for IFN-I to enable Th2 induction by DCs against Th2 Ag in vivo. Future work will address the wider role of IFN-I in Th2 inflammation, including during patent helminth infection in vivo.