Sensory Afferent Neurons Coordinate In Host Immune Responses To Citrobacter Rodentium

Background Neuro-immune communication is a vital component of regulating host immune responses to pathogens. Specialized sensory neurons have recently been described to detect bacterial pathogens in the skin, lung, and small intestine, inducing either maladaptive or host-protective responses. Here we assessed the role of sensory nociceptive neurons in the host response to the enteric pathogen Citrobacter rodentium. Methods Selective ablation of nociceptive neurons was accomplished using the Trpv1 agonist Resiniferatoxin (RTX) 10 days prior to C. rodentium infection of mice (C57BL/6). Results RTX-treated mice exhibited significantly increased bacterial burden 10 days post infection and delayed pathogen clearance compared to vehicle control mice. This reduced host-protective immune response was due to significantly reduced expression of IL-22, and recruitment of CD3+ T-cells into the colonic mucosa. This process appears to be TRPV1 dependent as TRPV1 KO mice experienced a similar delay in T-cell recruitment. Expression of pro-inflammatory cytokines in RTX-treated mice was significantly enhanced, and was associated with increased numbers of colonic T-cells 29 days p.i.. As previous studies identified the sensory neuropeptide CGRP as a regulator of host immune responses, we assessed the role of CGRP receptor signaling during C. rodentium infection. Antagonism of the CGRP receptor reduced expression of Il6, and Ifng, while bacterial burden and Il22 expression was not reduced compared to C. rodentium-infected vehicle-treated control mice. Conclusions Our data indicate that sensory nociceptive neurons exert a significant host protective role during C. rodentium infection that is independent of CGRP.