Ly6Chi and Ly6Clow blood monocytes from naïve and Heligmosomoides polygyrus bakeri infected mice

Alterations to monocyte output and function occur during infections that drive classical Th1-type inflammation. The degree to which the circulating monocyte compartment responds to infections that initiate alternative types of response is poorly understood. Here we describe a unique state of the monocyte compartment associated with type 2-favouring intestinal helminths. The adapted monocyte state in a type 2 setting was associated with an interferon-signature. Acquisition of this interferon-induced state provided helminth-infected animals with unappreciated systemic protection against secondary bacterial infection, but still allowed for the development of effective type-2 immunity. This pathway of monocyte education was completely distinct from that described in Th1-settings and involved an endogenous-bacteria-mediated induction of type I IFN that led to adaptive lymphocyte-dependent IFN- priming of monocytes. These findings reveal an IFN-driven mechanism of monocytes education that enables the host to be simultaneously protected against type-2 infections at barrier sites and type-1 infections in the circulation.