"Understanding host resistance to skin penetrating helminths"

E. Evonne Jean, Heather Rossi and De’Broski R. Herbert

Soil transmitted helminths (STH) cause chronic disease and significant morbidity in billions of people across the globe. Most STH species have an infectious third-stage larvae (iL3) that can directly penetrate the skin of its host to establish parasitism. Strongylodies ratti is a rodent specific gastrointestinal nematode that mimics key features of pathogenesis caused by the human parasite S. stercoralis and is used to understand mechanisms of Type 2 immunity. While considerable work has revealed the importance of hematopoietic cells including CD4 T cells, eosinophils, mast cells and innate lymphoid cells in host resistance, the role of non-hematopoietic cells remains less well understood. In particular, skin sensory neurons are known to serve key roles in immunity against microbial and fungal pathogens, but the role of neurons in immunity against STH infections is currently unexplored.  This gap is largely due to needle-based inoculation methods that bypass neurons innervating the epidermal and dermal layers of skin. To address this issue, we developed an infection system wherein the mouse footpad is transiently exposed to a saline bath of iL3, allowing natural penetration. Data show that wild-type mice acquire resistance to skin penetration by iL3 following prior exposure.  We asked whether the neuron cation channel transient receptor potential cation channel subfamily V member 1 (TRPV1), served an important role in host resistance to S. ratti.  Strikingly, mice lacking TRPV1, fail to acquire resistance and conversely mice allowing optogenetic stimulation of TRPV1 expressing neurons prior to infection show enhanced resistance. Future studies will determine the contributions of distinct skin innervating neuron subsets in augmenting host resistance through activation of CD4 T Cells, innate inflammatory cells, release of neuropeptides and/or Type 2 and Type 17 cytokines.