Abstract
During infection, recognition of pathogens and inflammatory cytokines skews hematopoiesis toward myeloid development, although the precise mechanisms responsible for this are unclear. In this study, we show that accelerated myeloid differentiation, known as emergency myelopoiesis, involves recognition of pathogen-associated molecular patterns by the common myeloid progenitor (CMP) and is dependent on type I IFN for monocyte/macrophage differentiation. Direct sensing of TLR agonists by CMP induced rapid proliferation and induction of myeloid-differentiation genes. Lack of type I IFN signaling in CMP abrogated macrophage differentiation in response to TLR stimuli, whereas exogenous type I IFN amplified this process. Mechanistically, TLR7 induced PI3K/mammalian target of rapamycin signaling in CMP, which was enhanced by type I IFN, and this pathway was essential for emergency myelopoiesis. This work identifies a novel mechanism by which TLR and type I IFN synergize to promote monocyte/macrophage development from hematopoietic progenitors, a process critical in triggering rapid immune responses during infection.