Neutrophil elastase-mediated increase in airway temperature during inflammation
Open accessAbstract
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.
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In acute illness, the normally nutrient-poor alveolus is flooded with nutrient-rich oedema, oxygen and temperature gradients are established, and host stress signalling molecules selectively promote the growth of potential pathogens.
“The normally nutrient-poor environment of the alveolus is flooded with nutrient-rich oedema,55 pockets of oxygen and heterogeneous temperature gradients are established,48,49 and the signalling molecules of the host stress response selectively promote the growth of potential pathogens.”
From The microbiome and critical illness (2016) · cites this paper as [49]
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References 44 · Cited by 30
- Authors
- Schmidt, A., Belaaouaj, A., Bissinger, R., Koller, G., Malleret, L., D'Orazio, C., Facchinelli, M., Schulte-Hubbert, B., Molinaro, A., Holst, O., Hammermann, J., Schniederjans, M., Meyer, K. C., Damkiaer, S., Piacentini, G., Assael, B., Bruce, K., Häußler, S., LiPuma, J. J., Seelig, J., Worlitzsch, D., & Döring, G.
- Affiliations
- Universitätsklinikum Tübingen (DE)
- Inserm (FR)
- King's College London (GB)
- Technische Universität Dresden (DE)
- University of Naples Federico II (IT)
- Research Center Borstel - Leibniz Lung Center (DE)
- Helmholtz Centre for Infection Research (DE)
- University of Wisconsin–Madison (US)
- Technical University of Denmark (DK)
- University of Verona (IT)
- University of Michigan (US)
- University of Basel (CH)
- Martin Luther University Halle-Wittenberg (DE)
- Corresponding author
- Worlitzsch, Dieter
- ORCID
- Venue
- Journal of Cystic Fibrosis
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 13
- Issue
- 6
- Pages
- 623-631
- ISSN
- 1569-1993 (ISSN-L)
- OpenAlex
- W2051055899
- Cited by
- 30
- References
- 44
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 4 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 4 · 2014: 1
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Cystic Fibrosis (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
- Funders
- DFG
- Inserm Avenir Program
- Fondation pour la Recherche Médicale (FRM)
- Agence Nationale de la Recherche (ANR)
- Contrats Projets Etat-Région (CPER)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- neutrophil elastase, airway temperature, Pseudomonas aeruginosa, mucus plugs, innate immunity, chronic airway infection, bacterial virulence
- MeSH terms
- Adolescent, Animals, Body Temperature, Child, Cystic Fibrosis, Disease Models, Animal, Female, Hot Temperature, Humans, Male, Mice, Inbred C57BL, Pseudomonas aeruginosa, Pseudomonas Infections, Respiratory Tract Infections, Case-Control Studies, Leukocyte Elastase, Mice
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