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 interrogated whether pain-sensing skin afferents marked by expression of the ion channel Transient Receptor Potential Vanilloid 1 (TRPV1) contributed to the detection and initiation of skin immunity against S. mansoni. Data show that percutaneous S. mansoni infection significantly reduced thermal pain sensitivity evoked by TRPV1+ neurons. Consistently, isolated skin sensory neurons from infected mice had significantly reduced calcium influx and neuropeptide release in response to the TRPV1 agonist capsaicin compared to neurons from naïve controls. Using gain- and loss-of-function approaches to test whether TRPV1+ neurons initiate host-protective responses revealed that TRPV1+ neurons limit S. mansoni skin entry and migration into the pulmonary tract. Moreover, TRPV1+ neurons were both necessary and sufficient to promote proliferation and cytokine production from dermal γδ T cells and CD4+ T helper cells, as well as to enhance neutrophil and monocyte recruitment to the skin. Taken together, this work suggests that S. mansoni may have evolved to manipulate TRPV1+ neuron activation as a countermeasure to limit IL-17-mediated inflammation, facilitating systemic dissemination and chronic parasitism.