Type I IFN-induced IFN-γ instructs monocyte-mediated systemic bacterial protection during type 2 intestinal helminth infection.

Alterations to monocyte output and function occur during infections driving T helper 1 (TH1)-type inflammation. The degree to which monocytes respond to infections initiating alternative types of responses is poorly understood. Here, we describe a distinct state of the monocyte compartment associated with type 2-polarizing intestinal helminths. Unexpectedly, the adapted monocyte state in a type 2 setting was associated with acquisition of an interferon (IFN) signature. This IFN-induced state provided helminth-infected animals with systemic protection against secondary bacterial infection and allowed for the development of effective type 2 immunity. This pathway of monocyte education was distinct from that in TH1 settings and involved an endogenous bacteria-mediated induction of type I IFN that led to adaptive lymphocyte-dependent IFN-γ priming of monocytes. These findings reveal an IFN-driven mechanism of monocyte education that enables the host to be simultaneously protected against type 2 infections at barrier sites and type 1 infections in the circulation.