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Nociceptor sensory neurons suppress neutrophil and γδ T cell responses in bacterial lung infections and lethal pneumonia.


ABSTRACT: Lung-innervating nociceptor sensory neurons detect noxious or harmful stimuli and consequently protect organisms by mediating coughing, pain, and bronchoconstriction. However, the role of sensory neurons in pulmonary host defense is unclear. Here, we found that TRPV1+ nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1+-neuron ablation increased survival, cytokine induction, and lung bacterial clearance. Nociceptors suppressed the recruitment and surveillance of neutrophils, and altered lung γδ T cell numbers, which are necessary for immunity. Vagal ganglia TRPV1+ afferents mediated immunosuppression through release of the neuropeptide calcitonin gene-related peptide (CGRP). Targeting neuroimmunological signaling may be an effective approach to treat lung infections and bacterial pneumonia.

SUBMITTER: Baral P 

PROVIDER: S-EPMC6263165 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Nociceptor sensory neurons suppress neutrophil and γδ T cell responses in bacterial lung infections and lethal pneumonia.

Baral Pankaj P   Umans Benjamin D BD   Li Lu L   Wallrapp Antonia A   Bist Meghna M   Kirschbaum Talia T   Wei Yibing Y   Zhou Yan Y   Kuchroo Vijay K VK   Burkett Patrick R PR   Yipp Bryan G BG   Liberles Stephen D SD   Chiu Isaac M IM  

Nature medicine 20180305 4


Lung-innervating nociceptor sensory neurons detect noxious or harmful stimuli and consequently protect organisms by mediating coughing, pain, and bronchoconstriction. However, the role of sensory neurons in pulmonary host defense is unclear. Here, we found that TRPV1<sup>+</sup> nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1<sup>+</sup>-neuron ablation increased survival, cytokine induction, and lung bacterial clearance. Nociceptors supp  ...[more]

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