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.
In the version of this article initially published, the line graph showing TNF-α levels in Fig. 2d was inadvertently duplicated. A graph of IL-6 levels should be shown in place of the duplication.These results were also incorrectly described in the main text, which originally stated: "At an early time point of infection (6 h), RTX-treated mice showed higher induction of total inflammatory-protein levels in the bronchoalveolar lavage fluid (BALF) (Fig. 2c), as well as levels of the cytokines TNF-α and IL-6, and the chemokine CXCL-1 (Fig. 2d)". This should instead read: "At an early time point of infection (6 h), RTX-treated mice showed higher induction of total inflammatory-protein levels in the bronchoalveolar lavage fluid (BALF) (Fig. 2c), as well as levels of the cytokine TNF-α and the chemokine CXCL-1 (Fig. 2d)".In the supplementary information initially posted online, incorrect bar graphs were presented in Supplementary Fig. 1b (VG, TRPV1+ data, top panel) and Supplementary Fig. 4b (DRG, CGRP+ data, middle panel).
Neutrophils play a critical role in the eradication of pathogenic organisms, particularly bacteria. However, in the septic patient the prolonged activation and accumulation of neutrophils may augment tissue and organ injury. This review discusses the different activation states and chemotaxis of neutrophils in septic patients. Neutrophil killing of bacteria and the formation of neutrophil extracellular traps represent important components of the innate immune response and they become dysregulated during sepsis, possibly through changes in their metabolism. Delayed neutrophil apoptosis may contribute to organ injury, or allow better clearance of pathogens. Neutrophils provide a friendly immune response to clear infections, but excessive activation and recruitment has the potential to turn them into potent foes.
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