Dataset Information

Sensory Nociceptive Neurons Contribute to Host Protection During Enteric Infection With Citrobacter rodentium.

ABSTRACT:

Background

Neurons are an integral component of the immune system that functions to coordinate responses to bacterial pathogens. Sensory nociceptive neurons that can detect bacterial pathogens are found throughout the body with dense innervation of the intestinal tract.

Methods

In this study, we assessed the role of these nerves in the coordination of host defenses to Citrobacter rodentium. Selective ablation of nociceptive neurons significantly increased bacterial burden 10 days postinfection and delayed pathogen clearance.

Results

Because the sensory neuropeptide CGRP (calcitonin gene-related peptide) regulates host responses during infection of the skin, lung, and small intestine, we assessed the role of CGRP receptor signaling during C rodentium infection. Although CGRP receptor blockade reduced certain proinflammatory gene expression, bacterial burden and Il-22 expression was unaffected.

Conclusions

Our data highlight that sensory nociceptive neurons exert a significant host protective role during C rodentium infection, independent of CGRP receptor signaling.

SUBMITTER: Ramirez VT

PROVIDER: S-EPMC7289549 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Sensory Nociceptive Neurons Contribute to Host Protection During Enteric Infection With Citrobacter rodentium.

Ramirez Valerie T VT Sladek Jessica J Godinez Dayn Romero DR Rude Kavi M KM Chicco Pamela P Murray Kaitlin K Brust-Mascher Ingrid I Gareau Melanie G MG Reardon Colin C

The Journal of infectious diseases 20200601 12

<h4>Background</h4>Neurons are an integral component of the immune system that functions to coordinate responses to bacterial pathogens. Sensory nociceptive neurons that can detect bacterial pathogens are found throughout the body with dense innervation of the intestinal tract.<h4>Methods</h4>In this study, we assessed the role of these nerves in the coordination of host defenses to Citrobacter rodentium. Selective ablation of nociceptive neurons significantly increased bacterial burden 10 days ...[more]

PMID: 31960920

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Project description:Mucosal immunity is critical to host protection from enteric pathogens and must be carefully controlled to prevent immunopathology. Regulation of immune responses can occur through a diverse range of mechanisms including bi-directional communication with the neurons. Among which include specialized sensory neurons that detect noxious stimuli due to the expression of transient receptor potential vanilloid receptor 1 (TRPV1) ion channel and have a significant role in the coordination of host-protective responses to enteric bacterial pathogens. Here we have used the mouse-adapted attaching and effacing pathogen Citrobacter rodentium to assess the specific role of the TRPV1 channel in coordinating the host response. TRPV1 knockout (TRPV1 -/- ) mice had a significantly higher C. rodentium burden in the distal colon and fecal pellets compared to wild-type (WT) mice. Increased bacterial burden was correlated with significantly increased colonic crypt hyperplasia and proliferating intestinal epithelial cells in TRPV1 -/- mice compared to WT. Despite the increased C. rodentium burden and histopathology, the recruitment of colonic T cells producing IFNγ, IL-17, or IL-22 was similar between TRPV1 -/- and WT mice. In evaluating the innate immune response, we identified that colonic neutrophil recruitment in C. rodentium infected TRPV1 -/- mice was significantly reduced compared to WT mice; however, this was independent of neutrophil development and maturation within the bone marrow compartment. TRPV1 -/- mice were found to have significantly decreased expression of the neutrophil-specific chemokine Cxcl6 and the adhesion molecules Icam1 in the distal colon compared to WT mice. Corroborating these findings, a significant reduction in ICAM-1 and VCAM-1, but not MAdCAM-1 protein on the surface of colonic blood endothelial cells from C. rodentium infected TRPV1 -/- mice compared to WT was observed. These findings demonstrate the critical role of TRPV1 in regulating the host protective responses to enteric bacterial pathogens, and mucosal immune responses.Author summaryNeuroimmune communications are vital in regulating the immune response to invading pathogens. Here, we show that during a gastrointestinal infection, pain-sensing neuronal fibers can modulate the immune response to recruit phagocytic neutrophils via upregulation of cell adhesion molecules on local blood endothelial cells. This research elucidates a novel impact of the pain-sensing ion channel, TRPV1, on host-pathogen interactions in the gastrointestinal tract as well as a potential methodology for modulating the immune response during enteric infections.

Dataset Information

Sensory Nociceptive Neurons Contribute to Host Protection During Enteric Infection With Citrobacter rodentium.

Background

Methods

Results

Conclusions

Publications

Sensory Nociceptive Neurons Contribute to Host Protection During Enteric Infection With Citrobacter rodentium.

Similar Datasets

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