Gut-Innervating Nociceptor Neurons Regulate Peyer's Patch Microfold Cells and SFB Levels to Mediate Salmonella Host Defense.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lai, NY; Musser, MA; Pinho-Ribeiro, FA; Baral, P; Jacobson, A; Ma, P; Potts, DE; Chen, Z; Paik, D; Soualhi, S; Yan, Y; Misra, A; Goldstein, K; Lagomarsino, VN; Nordstrom, A; Sivanathan, KN; Wallrapp, A; Kuchroo, VK; Nowarski, R; Starnbach, MN; Shi, H; Surana, NK; An, D; Wu, C; Huh, JR; Rao, M; Chiu, IM

Published Date

  • January 9, 2020

Published In

Volume / Issue

  • 180 / 1

Start / End Page

  • 33 - 49.e22

PubMed ID

  • 31813624

Pubmed Central ID

  • 31813624

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2019.11.014

Language

  • eng

Conference Location

  • United States