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

• Published in: Nature medicine Vol. 24; no. 4; pp. 417 - 426
• Main Authors: Baral, Pankaj, Umans, Benjamin D, Li, Lu, Wallrapp, Antonia, Bist, Meghna, Kirschbaum, Talia, Wei, Yibing, Zhou, Yan, Kuchroo, Vijay K, Burkett, Patrick R, Yipp, Bryan G, Liberles, Stephen D, Chiu, Isaac M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.05.2018; Nature Publishing Group
• Subjects: 13/21; 13/51; 14/63; 14/69; 631/250/255; 631/250/371; 631/326/41; 631/378/371; 64/60; 96/106; 96/31; Ablation; Biomedicine; Body temperature; Bronchoconstriction; Bronchopulmonary infection; Calcitonin; Calcitonin gene-related peptide; Cancer Research; Capsaicin receptors; Cell survival; Critical care; Defense; Drug dosages; Ganglia; Heat; Hospitals; Immunity (Disease); Immunosuppression; Infectious Diseases; Innate immunity; Leukocytes (neutrophilic); Lungs; Lymphocytes; Lymphocytes T; Medicine; Metabolic Diseases; Molecular Medicine; Neurons; Neurosciences; Neutrophils; Nociceptors; Nosocomial infections; Pain perception; Pathogens; Pneumonia; Sensory neurons; Staphylococcus infections; Streptococcus infections; Toxins; Vagus nerve
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.4501

Nociceptor sensory neurons suppress innate immunity during bacterial lung infection. 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.