Papers of the Week

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 (AVP) production remains largely unknown. Here, we characterize the induction and regulation of AVPs following skin injury and identify a key role of the transient receptor potential cation channel subfamily V member 1 (TRPV1) in this process. Transcriptional and phenotypic profiling of cutaneous wounds revealed that skin injury induces high levels of AVPs in both mice and humans. Remarkably, pharmacological and genetic ablation of TRPV1-mediated nociception abrogated induction of AVPs including Oas2, Oasl2, and Isg15 following skin injury in mice. Conversely, stimulation of TRPV1 nociceptors was sufficient to induce antiviral protein production involving the CD301b cells-interleukin (IL)-27-mediated signaling pathway. Using IL-27 receptor knockout mice, we demonstrate that IL-27 signaling is required in the induction of AVPs following skin injury. Finally, loss of TRPV1 signaling leads to increased viral infectivity of herpes simplex virus. Together, our data indicate that TRPV1 signaling ensures skin antiviral competence upon wounding.