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Papers of the Week


Papers: 7 Dec 2019 - 13 Dec 2019


Animal Studies


2020 Jan 09


Cell


180


1

Editor's Pick

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

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, et al.
Cell. 2020 Jan 09; 180(1):33-49.e22.
PMID: 31813624.

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.