Neutrophil elastase-mediated increase in airway temperature during inflammation

Area of Science:

• Pulmonary Medicine
• Microbiology
• Immunology

Background:

• The physiological mechanisms generating elevated temperatures during airway infections remain unclear.
• Innate immune responses are hypothesized to increase airway luminal temperature during pulmonary infections.

Purpose of the Study:

• To investigate the source of elevated airway temperature in cystic fibrosis (CF) patients.
• To determine the role of neutrophil elastase in temperature regulation during infection.
• To assess the impact of temperature on Pseudomonas aeruginosa virulence.

Main Methods:

• Measured exhaled air temperature in CF patients.
• Utilized a mouse pouch inflammatory model with neutrophil elastase-deficient mice.
• Assessed Pseudomonas aeruginosa growth and gene expression at different temperatures using plating and RNAseq.

Main Results:

• CF patients with chronic infections exhibited mucus plug temperatures around 38°C.
• Neutrophil elastase:α1-proteinase inhibitor complex formation was implicated in local temperature increases.
• Increased P. aeruginosa virulence traits and cell wall alterations were observed at 38°C compared to 30°C under anaerobic conditions.

Conclusions:

• Neutrophil elastase plays a role in increasing airway temperature.
• Elevated airway temperatures may contribute to the selection and persistence of P. aeruginosa in chronic CF infections.