| Literature DB >> 31813624 |
Nicole Y Lai1, Melissa A Musser2, Felipe A Pinho-Ribeiro1, Pankaj Baral1, Amanda Jacobson1, Pingchuan Ma1, David E Potts1, Zuojia Chen3, Donggi Paik1, Salima Soualhi4, Yiqing Yan1, Aditya Misra1, Kaitlin Goldstein1, Valentina N Lagomarsino1, Anja Nordstrom5, Kisha N Sivanathan6, Antonia Wallrapp6, Vijay K Kuchroo6, Roni Nowarski6, Michael N Starnbach7, Hailian Shi8, Neeraj K Surana9, Dingding An4, Chuan Wu3, Jun R Huh1, Meenakshi Rao4, Isaac M Chiu10.
Abstract
Gut-innervating nociceptor sensory neurons respond to noxious stimuli by initiating protective responses including pain and inflammation; however, their role in enteric infections is unclear. Here, we find that nociceptor neurons critically mediate host defense against the bacterial pathogen Salmonella enterica serovar Typhimurium (STm). Dorsal root ganglia nociceptors protect against STm colonization, invasion, and dissemination from the gut. Nociceptors regulate the density of microfold (M) cells in ileum Peyer's patch (PP) follicle-associated epithelia (FAE) to limit entry points for STm invasion. Downstream of M cells, nociceptors maintain levels of segmentous filamentous bacteria (SFB), a gut microbe residing on ileum villi and PP FAE that mediates resistance to STm infection. TRPV1+ nociceptors directly respond to STm by releasing calcitonin gene-related peptide (CGRP), a neuropeptide that modulates M cells and SFB levels to protect against Salmonella infection. These findings reveal a major role for nociceptor neurons in sensing and defending against enteric pathogens.Entities:
Keywords: M cell; Peyer's patch; SFB; Salmonella; gut microbiome; host-pathogen; mucosal immunology; neuro-immune; nociceptor; segmentous filamentous bacteria
Mesh：
Year: 2019 PMID： 31813624 PMCID： PMC6954329 DOI： 10.1016/j.cell.2019.11.014
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582