Exploring cutaneous neuro-immune networks during helminth infection

Abstract

Abstract Sensory nociceptive neurons serve important roles in regulation of cutaneous inflammation directed against microbial and fungal pathogens, but whether neurons serve any role in protective immunity against skin penetrating helminths remains unknown. In this study, we sought to identify the key factors responsible for blocking parasite entry of host skin. Data show that CD4 T cells were essential for restricting parasite entry of the skin during secondary infection, but this resistance was not dependent upon the key TH2 transcription factor Signal Transducer And Activator Of Transcription 6 (STAT6). Interestingly, STAT6 deficient mice generated high levels of TH17 associated cytokines, the latter of which are known to be induced by skin nociceptors. To determine whether skin neurons could prime host protective immunity, we used an optogenetic approach that allowed pre-activation of neurons at the site of skin inoculation that expressed transient receptor potential cation channel subfamily V member 1 (TRPV1). Strikingly, preemptive activation of TRPV1 neurons led to a significant inhibition of parasite entry. Ongoing studies are designed to understand whether depletion of TRPV1 skin neurons impairs immunity and whether skin protection relies upon TH17 dependent immunity. Supported by grants from NIH (R01 AI095289 and R01 GM083204) and NSF GFRP (Fellow ID:2020297782)