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

伤害感受器感觉神经元抑制细菌性肺部感染和致死性肺炎中的中性粒细胞和γδT细胞反应

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作者:Pankaj Baral, Benjamin D Umans, Lu Li, Antonia Wallrapp, Meghna Bist, Talia Kirschbaum, Yibing Wei, Yan Zhou, Vijay K Kuchroo, Patrick R Burkett, Bryan G Yipp, Stephen D Liberles, Isaac M Chiu

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.

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