Joshi, Prabhu Raj and Adhikari, Sandeep and Onah, Chinemerem and Carrier, Camille and Judd, Abigail and Mack, Matthias and Baral, Pankaj (2024) Lung-innervating nociceptor sensory neurons promote pneumonic sepsis during carbapenem-resistant Klebsiella pneumoniae lung infection. SCIENCE ADVANCES, 10 (36): eadl6162. ISSN 2375-2548,
Full text not available from this repository. (Request a copy)Abstract
Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes Gram-negative lung infections and fatal pneumonic sepsis for which limited therapeutic options are available. The lungs are densely innervated by nociceptor sensory neurons that mediate breathing, cough, and bronchoconstriction. The role of nociceptors in defense against Gram-negative lung pathogens is unknown. Here, we found that lung-innervating nociceptors promote CRKP pneumonia and pneumonic sepsis. Ablation of nociceptors in mice increased lung CRKP clearance, suppressed trans-alveolar dissemination of CRKP, and protected mice from hypothermia and death. Furthermore, ablation of nociceptors enhanced the recruitment of neutrophils and Ly6(Chi) monocytes and cytokine induction. Depletion of Ly6(Chi) monocytes, but not of neutrophils, abrogated lung and extrapulmonary CRKP clearance in ablated mice, suggesting that Ly6(Chi) monocytes are a critical cellular population to regulate pneumonic sepsis. Further, neuropeptide calcitonin gene-related peptide suppressed the induction of reactive oxygen species in Ly6(Chi )monocytes and their CRKP-killing abilities. Targeting nociceptor signaling could be a therapeutic approach for treating multidrug-resistant Gram-negative infection and pneumonic sepsis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RISK-FACTORS; BONE-MARROW; CELLS; EXPRESSION; HYPERREACTIVITY; MOBILIZATION; RECRUITMENT; NEUTROPHILS; MECHANISMS; CHEMOKINE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Jan 2026 06:49 |
| Last Modified: | 14 Jan 2026 07:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64546 |
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