1 Center for Systems Microbiology, Department of Systems Biology, Technical University of Denmark2 Department of Systems Biology, Technical University of Denmark3 University Clinic Tübingen4 Centre International de Recherche en Infectiologie5 King’s College London6 Department of Pediatrics, Verona7 Ospedale Civile Maggiore, Verona8 Dresden University of Technology9 University of Naples Federico II10 Airway Research Center North11 unknown
Background How elevated temperature is generated during airway infections represents a hitherto unresolved physiological question. We hypothesized that innate immune defence mechanisms would increase luminal airway temperature during pulmonary infection. Methods We determined the temperature in the exhaled air of cystic fibrosis (CF) patients. To further test our hypothesis, a pouch inflammatory model using neutrophil elastase-deficient mice was employed. Next, the impact of temperature changes on the dominant CF pathogen Pseudomonas aeruginosa growth was tested by plating method and RNAseq. Results Here we show a temperature of ~ 38 °C in neutrophil-dominated mucus plugs of chronically infected CF patients and implicate neutrophil elastase:α1-proteinase inhibitor complex formation as a relevant mechanism for the local temperature rise. Gene expression of the main pathogen in CF, P. aeruginosa, under anaerobic conditions at 38 °C vs 30 °C revealed increased virulence traits and characteristic cell wall changes. Conclusion Neutrophil elastase mediates increase in airway temperature, which may contribute to P. aeruginosa selection during the course of chronic infection in CF.
Journal of Cystic Fibrosis, 2014, Vol 13, Issue 6, p. 623-631