Abstract
Immunity against skin-invasive pathogens requires mechanisms that rapidly detect, repel or immobilize the infectious agent. While bacteria often cause painful cutaneous reactions, host skin invasion by the human parasitic helminth Schistosoma mansoni often goes unnoticed. This study investigated the role of pain-sensing skin afferents that express the ion channel Transient Receptor Potential Vanilloid 1 (TRPV1) in the detection and initiation of skin immunity against S. mansoni . Data show that mice infected with S. mansoni have reduced behavioral responses to painful stimuli and sensory neurons exposed from infected mice have significantly less calcium influx and neuropeptide release in response to the TRPV1 agonist capsaicin. Using both gain- and loss-of-function approaches, data show that TRPV1+ neurons are critical regulators of S. mansoni survival during migration from the skin into the pulmonary tract. Moreover, TRPV1+ neurons were both necessary and sufficient to promote proliferation and cytokine production from dermal γδ T cells as well as neutrophil and monocyte skin accumulation post-infection. These results suggest a model in which S. mansoni may have evolved to inhibit TRPV1+ neuron activation as a countermeasure that limits IL-17-mediated inflammation, facilitating systemic dissemination and chronic parasitism. ONE SENTENCE SUMMARY: The parasitic helminth Schistosoma mansoni averts IL-17-dependent protective immunity by suppressing skin-innervating TRPV1+ neurons.