154 Nociceptor sensory neurons promote CD8 T cell response to VACV infection

CD8+ T cells have a critical role in antiviral immunity peripheral tissues, including skin. Using cutaneous vaccinia virus (VACV) infection model, we demonstrate that VACV immunization (with or with heterologous sequences) by skin scarification/ epidermal disruption (ss/ed) protected mice far more effectively against lethal respiratory challenge other viruses than routes of delivery intramuscular (i.m.), subcutaneous (s.c.) and intradermal (i.d.). However, the mechanism which scarification provides such superior CD8 host defense is still being explored. For this study, asked whether sensory neurons might influence outcome vaccination disruption. We found neuropeptide calcitonin gene-related peptide (CGRP) was preferentially released upon scarification/epidermal when compared to immunization. further determined targeted ablation Trpv1+-neurons (sensory), are principal producer CGRP involved pain perception, controls magnitude cell priming expansion VACV-immunized mice. Moreover, continuous injection boosted response immunized though route. These findings important implications for our understanding protective immune at epithelial interfaces neurons, thereby potentially suggesting new targetable pathways poxviral vaccine design.