Abstract

Airway microenvironment played an important role in the progression of chronic respiratory disease. Here we showed that standardized pondus hydrogenii (pH) of exhaled breath condensate (EBC) of bronchiectasis patients was significantly lower than that of controls and was significantly correlated with bronchiectasis severity index (BSI) scores and disease prognosis. EBC pH was lower in severe patients than that in mild and moderate patients. Besides, acidic microenvironment deteriorated Pseudomonas aeruginosa (P. aeruginosa) pulmonary infection in mice models. Mechanistically, acidic microenvironment increased P. aeruginosa outer membrane vesicles (PA_OMVs) released and boosted it induced the activation of interferon regulatory factor3 (IRF3)-interferonβ (IFN-β) signalling pathway, ultimately compromised the anti-bacteria immunity. Targeted knockout of IRF3 or type 1 interferon receptor (IFNAR1) alleviated lung damage and lethality of mice after P. aeruginosa infection that aggravated by acidic microenvironment. Together, these findings identified airway acidification impaired host resistance to P. aeruginosa infection by enhancing it induced the activation of IRF3-IFN-β signalling pathway. Standardized EBC pH may be a useful biomarker of disease severity and a potential therapeutic target for the refractory P. aeruginosa infection. The study also provided one more reference parameter for drug selection and new drug discovery for bronchiectasis.

Details

Title
Airway acidification impaired host defense against Pseudomonas aeruginosa infection by promoting type 1 interferon β response
Author
Liu, Yang 1 ; Ying-Zhou, Xie 1 ; Yi-Han, Shi 1 ; Yang, Ling 1 ; Xiao-Yang, Chen 2 ; Ling-Wei, Wang 3 ; Jie-Ming Qu 4   VIAFID ORCID Logo  ; Weng, Dong 1 ; Xiao-Jian, Wang 5 ; Hai-Peng, Liu 6 ; Bao-Xue Ge 6 ; Jin-Fu, Xu 1   VIAFID ORCID Logo 

1  Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai, People’s Republic of China 
2  Department of Pulmonary and Critical Care Medicine, Second Affiliated Hospitial of Fujian Medical University, Respiratory Medicine Center of Fujian Province, Fujian, People’s Republic of China 
3  Department of Respiratory Diseases and Critic Care Unit, Shenzhen Institute of Respiratory Disease, Shenzhen Key Laboratory of Respiratory Disease, Shenzhen People’s Hospital, Shenzhen, People’s Republic of China 
4  Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China 
5  Institute of Immunology and Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, People’s Republic of China 
6  Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China 
Pages
2132-2146
Publication year
2022
Publication date
Dec 2022
Publisher
Taylor & Francis Ltd.
e-ISSN
22221751
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/22221751.2022.2110524
ProQuest document ID
2748035281
Copyright
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.