The commensal skin microbiota triggers type I IFN-dependent innate repair responses in injured skin.

Abstract

Skin wounds heal by coordinated induction of inflammation and tissue repair, but the initiating events are poorly defined. Here we uncover a fundamental role of commensal skin microbiota in this process and show that it is mediated by the recruitment and the activation of type I interferon (IFN)-producing plasmacytoid DC (pDC). Commensal bacteria colonizing skin wounds trigger activation of neutrophils to express the chemokine CXCL10, which recruits pDC and acts as an antimicrobial protein to kill exposed microbiota, leading to the formation of CXCL10-bacterial DNA complexes. 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 early T cell-independent wound repair responses, mediated by macrophages and fibroblasts that produce major growth factors required for healing. These findings identify a key function of commensal microbiota in driving a central innate wound healing response of the skin.

• Authors: Jeremy Di Domizio, Cyrine Belkhodja, Pauline Chenuet, Anissa Fries, Timothy Murray, Paula Marcos Mondéjar, Olivier Demaria, Curdin Conrad, Bernhard Homey, Sabine Werner, Daniel E Speiser, Bernhard Ryffel, Michel Gilliet
• Journal: Nature immunology (Nat Immunol) Vol. 21 Issue 9 Pg. 1034-1045 (09 2020) ISSN: 1529-2916 [Electronic] United States
• PMID: 32661363 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CXCL10
• Interferon Type I

Topics

• Animals
• Cells, Cultured
• Chemokine CXCL10 (metabolism)
• Dendritic Cells (immunology)
• Fibroblasts (immunology)
• Humans
• Immunity, Innate
• Inflammation
• Interferon Type I (metabolism)
• Macrophages (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microbiota (immunology)
• Neutrophils (immunology)
• Skin (immunology, pathology)
• Symbiosis
• Wound Healing