Skin Injury Activates TRPV1+ Nociceptive Fibers to Stimulate a Rapid Innate Antiviral Protein Response

The skin serves as the interface between the body and the environment and plays a fundamental role in innate antimicrobial host immunity.  Antiviral proteins are part of the innate host defense system and provide protection against viral pathogens.  How breach of the skin barrier influences innate antiviral protein production remains largely unknown.  Here, we identify and characterize the induction and regulation of antiviral proteins following skin injury.  Transcriptional and phenotypic profiling of cutaneous wounds revealed that skin injury induces high levels of antiviral proteins in both mice and humans, and interleukin (IL)-27 was found to be necessary and sufficient to induce this pattern of expression.  Notably, we here link the IL-27-mediated antiviral protein response to a neuro-immune axis.  We herein identify how damage to the skin barrier elicits cutaneous nociceptive signaling to activate innate antiviral immune responses.  Remarkably, pharmacology or genetic ablation of TRPV1-mediated nociception unveiled that TRPV1 signaling contributes significantly to the induction of antiviral proteins Oas2, Oasl2, and Isg15 via IL-27 in vivo, suggesting that nociception promotes skin antiviral competence through activation of antiviral signaling pathways upon wounding.