Dataset Information

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

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.

SUBMITTER: Lai NY

PROVIDER: S-EPMC6954329 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Lai Nicole Y NY Musser Melissa A MA Pinho-Ribeiro Felipe A FA Baral Pankaj P Jacobson Amanda A Ma Pingchuan P Potts David E DE Chen Zuojia Z Paik Donggi D Soualhi Salima S Yan Yiqing Y Misra Aditya A Goldstein Kaitlin K Lagomarsino Valentina N VN Nordstrom Anja A Sivanathan Kisha N KN Wallrapp Antonia A Kuchroo Vijay K VK Nowarski Roni R Starnbach Michael N MN Shi Hailian H Surana Neeraj K NK An Dingding D Wu Chuan C Huh Jun R JR Rao Meenakshi M Chiu Isaac M IM

Cell 20191205 1

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) ce ...[more]

PMID: 31813624

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Project description:ObjectiveTo investigate the dynamic regulation of self-assembled aggregations (SAA) in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying.MethodsThe effects of SAA on berberine (Ber) absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer's patches (PPs). The expression levels of ZO-1, Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction (TJ) between intestinal epithelium cells. The expression levels of T-box-containing protein expressed in T cells, signal transducers and activators of tranion-6, retinoic acid receptor-related orphan receptor γt and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) in PPs were evaluated by immunohistochemistry, to reflect the differentiation of T lymphocyte in PPs to helper T (Th) cell 1, Th2, Th17 and regulatory T (Treg) cell. To confirm the correlation between SAA in Coptidis Rhizoma decoction, PPs-associated immunity and intestinal epithelium permeability, SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression.ResultsSAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment, with the participation of PPs. The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs. The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation, inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression.ConclusionSAA can improve the Ber absorption in small intestine, through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression. These findings might enlighten the research of traditional Chinese medicine decoction.

Dataset Information

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

Publications

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

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