Neutrophil elastase-mediated increase in airway temperature during inflammation.
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.


CONCLUSIONS
Neutrophil elastase mediates increase in airway temperature, which may contribute to P. aeruginosa selection during the course of chronic infection in CF.
Institute of Medical Microbiology and Hygiene, German Center for Infection Research, University Clinic Tübingen, Germany.
Annika
A
Schmidt
INSERM U-1111, Centre International de Recherche en Infectiologie (CIRI), Lyon, France.
Azzaq
A
Belaaouaj
Institute of Medical Microbiology and Hygiene, German Center for Infection Research, University Clinic Tübingen, Germany.
Rosi
R
Bissinger
King's College, London, England.
Garrit
G
Koller
INSERM U-1111, Centre International de Recherche en Infectiologie (CIRI), Lyon, France.
Laurette
L
Malleret
Department of Pediatrics, Verona, Italy.
Ciro
C
D'Orazio
Ospedale Civile Maggiore, Verona, Italy.
Martino
M
Facchinelli
Medical Clinic und Policlinic I Pneumology, Technical University Dresden, Dresden, Germany.
Bernhard
B
Schulte-Hubbert
Department of Chemical Sciences, Università di Napoli Federico II, Italy.
Antonio
A
Molinaro
Research Center Borstel, Center for Medicine and Biosciences, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Borstel, Germany.
Otto
O
Holst
Department of Pediatrics, Technical University Dresden, Dresden, Germany.
Jutta
J
Hammermann
Helmholtz-Centre for Infection Research, Braunschweig, Germany.
Monika
M
Schniederjans
University of Wisconsin School of Medicine, Madison, USA.
Keith C
KC
Meyer
Department of Systems Biology and Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Soeren
S
Damkiaer
Ospedale Civile Maggiore, Verona, Italy.
Giorgio
G
Piacentini
Department of Pediatrics, Verona, Italy.
Baroukh
B
Assael
King's College, London, England.
Kenneth
K
Bruce
Research Center Borstel, Center for Medicine and Biosciences, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Borstel, Germany.
Susanne
S
Häußler
Department of Paediatrics, University of Michigan, Ann Arbor, USA.
John J
JJ
LiPuma
Biophysical Chemistry, University of Basel, Basel Switzerland.
Joachim
J
Seelig
Institute of Hygiene, University of Halle, Germany. Electronic address: dieter.worlitzsch@uk-halle.de.
Dieter
D
Worlitzsch
Institute of Medical Microbiology and Hygiene, German Center for Infection Research, University Clinic Tübingen, Germany.
Gerd
G
Döring
D000293:Adolescent; D000818:Animals; D001831:Body Temperature; D016022:Case-Control Studies; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications / Q000201:enzymology*; D004195:Disease Models, Animal; D005260:Female; D006358:Hot Temperature; D006801:Humans; D019272:Leukocyte Elastase / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa; D012141:Respiratory Tract Infections / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology
D019272:Leukocyte Elastase
Inflammation; Neutrophil elastase; Pseudomonas aeruginosa; Temperature