Skin wounds heal by the coordinated induction of inflammation and tissue repair responses, but the initiating events are poorly defined. Here we uncover a fundamental role of the commensal skin microbiota in this process and show that it is mediated by the recruitment and the activation of type I IFN-producing plasmacytoid DC (pDC). In fact, the commensal bacteria colonizing skin wounds trigger activation of neutrophils to express CXCL10. CXCL10 recruits pDC and acts as an antimicrobial protein that kills the exposed microbiota, leading to the formation of complexes with bacterial DNA. These complexes and not complexes with host-derived DNA activate pDC to produce type I IFNs, which accelerate wound closure by triggering skin inflammation and an early T cell-independent wound repair response mediated by macrophages and fibroblasts that produce major growth factors required for healing. These findings identify a key role of commensal microbiota in driving a central innate wound healing response of the skin.

Commensal microbiota trigger type I IFN-dependent innate wound repair responses in injured skin