Pseudomonas aeruginosa Modulates the Antiviral Response of Bronchial Epithelial Cells

Frontiers in Immunology

Dao Nguyen¹  Alexander H. Dalpke²  Marcus A. Mall³  Lauren Byrnes⁴  Julia Kantorek⁴  Michael Sörensen⁷  Felix Lasitschka⁹  Heike Zabeck^1,10  Sébastien Boutin^1,11 

[1] 0Department of Medicine, McGill University, Montreal, QC, Canada;1Institute of Medical Microbiology and Hygiene, Medical Faculty, Technische Universität Dresden, Dresden, Germany;Berlin Institute of Health (BIH), Berlin, Germany;Department of Infectious Diseases, Medical Microbiology and Hygiene, University Hospital Heidelberg, Heidelberg, Germany;Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany;Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany;Laboratory Enders and Partners, Stuttgart, Germany;Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada;TI Biobanking, German Centre for Infection Research (DZIF), Heidelberg, Germany;Thoraxklinik, University Hospital Heidelberg, Heidelberg, Germany;Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University Hospital Heidelberg, Heidelberg, Germany;

关键词: Pseudomonas aeruginosa;    cystic fibrosis;    virus;    antiviral response;    interferon;    protease;   

DOI  :  10.3389/fimmu.2020.00096

来源: DOAJ

【 摘 要 】

Cystic fibrosis (CF) patients frequently acquire Pseudomonas aeruginosa infections that have been associated with a bad prognosis and an increased rate of pulmonary exacerbations. Respiratory viruses can cause exacerbations in chronic pulmonary diseases including COPD or asthma and have been suggested to contribute to exacerbations also in CF. In this study we investigated a possible link between P. aeruginosa infection and susceptibility to respiratory viruses. We show that P. aeruginosa is able to block the antiviral response of airway epithelial cells thereby promoting virus infection and spread. Mechanistically, P. aeruginosa secretes the protease AprA in a LasR dependent manner, which is able of directly degrading epithelial-derived IFNλ resulting in inhibition of IFN signaling. In addition, we correlate the virus infection status of CF patients with the ability of patients' P. aeruginosa isolates to degrade IFNλ. In line with this, the infection status of CF patients correlated significantly with the amount of respiratory viruses in sputum. Our data suggest that the interplay between P. aeruginosa and respiratory virus infections might partially explain the association of increased rates of pulmonary exacerbations and P. aeruginosa infections in CF patients.

【 授权许可】

Unknown