Nociceptor Neurons are Involved in the Host Response to Escherichia coli Urinary Tract Infection

"Background: Urinary tract infections (UTIs) can evoke a rapid host response leading to bladder inflammation and epithelium damage. Neuroimmune interactions are critical for regulating immune function in mucosal tissues. The role of nociceptor neurons in bladder host defense has not been well defined. The present study aimed to investigate the role of nociceptor neurons on UTIs in bladder.Methods: Female C57BL/6J mice was treated with high dose of capsaicin, a high-affinity TRPV1 agonist, to ablate nociceptor neurons. Bladder inflammation, barrier epithelial function and bladder immune cell infiltration were assessed after UPEC infection. The level of neuropeptide calcitonin gene-related peptide (CGRP) in infected bladder was detected. The effects of CGRP on neutrophils and macrophages were evaluated both in vitro and in vivo.Results: UPEC and its pathogenic factor lipopolysaccharide (LPS) could directly excite nociceptor neurons, releasing CGRP into infected bladder which suppressed the recruitment of neutrophils, the polarization of macrophages and the killing function to UPEC. Both Botulinum neurotoxin A (BoNT/A) and BIBN4096 (CGRP antagonism) blocked neuronal inhibition, and prevented against UPEC infection.Conclusion: The present study showed a novel mechanism by which UPEC stimulated the secretion of CGRP from nociceptor neurons to suppress innate immunity. Thus, blocking neuro-immune suppressive effect may be a potential strategy to treat UTIs.Keywords: Urinary tract infection, CGRP, Nociceptor neurons, UPEC."