Cargando…

Pseudomonas aeruginosa Induces Interferon-β Production to Promote Intracellular Survival

Pseudomonas aeruginosa (PA) is known as one kind of extracellular pathogens. However, more evidence showed that PA encounters the intracellular environment in different mammalian cell types. Little is known of innate immune factors modulating intracellular PA survival. In the present study, we propo...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Ling, Zhang, Yu-Wei, Liu, Yang, Xie, Ying-Zhou, Weng, Dong, Ge, Bao-Xue, Liu, Hai-Peng, Xu, Jin-Fu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603546/
https://www.ncbi.nlm.nih.gov/pubmed/36190409
http://dx.doi.org/10.1128/spectrum.01550-22
_version_ 1784817578548396032
author Yang, Ling
Zhang, Yu-Wei
Liu, Yang
Xie, Ying-Zhou
Weng, Dong
Ge, Bao-Xue
Liu, Hai-Peng
Xu, Jin-Fu
author_facet Yang, Ling
Zhang, Yu-Wei
Liu, Yang
Xie, Ying-Zhou
Weng, Dong
Ge, Bao-Xue
Liu, Hai-Peng
Xu, Jin-Fu
author_sort Yang, Ling
collection PubMed
description Pseudomonas aeruginosa (PA) is known as one kind of extracellular pathogens. However, more evidence showed that PA encounters the intracellular environment in different mammalian cell types. Little is known of innate immune factors modulating intracellular PA survival. In the present study, we proposed that interferon-β (IFN-β) is beneficial to the survival of PA in the cytoplasm of macrophages. Furthermore, we found that interleukin-1β (IL-1β) induced by PA suppresses IFN-β response driven by the cGAS-STING-TBK1 pathway. Mechanistically, IL-1β decreased the production of cyclic GMP-AMP (cGAMP) by activating AKT kinase. cGAMP is necessarily sufficient to stimulate the transcription of IFN-β via the STING adaptor-TBK1 kinase-IRF3 transcription factor axis. Thus, our findings uncovered a novel module for PA intracellular survival involving IFN-β production restricted by IL-1β and provided a strong rationale for a potential clinical strategy against pulmonary PA infection patients. IMPORTANCE The link between innate immunity and intracellular Pseudomonas aeruginosa is unclear. Our studies illuminated the role of interferon-β (IFN-β) in remote intracellular PA infection. Furthermore, our experimental evidence also indicated that IL-1β is a negative regulator of IFN-β production and, in particular, P. aeruginosa infection. The inhibition of IFN-β may be used as a potential therapeutic method against pulmonary PA infection.
format Online
Article
Text
id pubmed-9603546
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Society for Microbiology
record_format MEDLINE/PubMed
spelling pubmed-96035462022-10-27 Pseudomonas aeruginosa Induces Interferon-β Production to Promote Intracellular Survival Yang, Ling Zhang, Yu-Wei Liu, Yang Xie, Ying-Zhou Weng, Dong Ge, Bao-Xue Liu, Hai-Peng Xu, Jin-Fu Microbiol Spectr Research Article Pseudomonas aeruginosa (PA) is known as one kind of extracellular pathogens. However, more evidence showed that PA encounters the intracellular environment in different mammalian cell types. Little is known of innate immune factors modulating intracellular PA survival. In the present study, we proposed that interferon-β (IFN-β) is beneficial to the survival of PA in the cytoplasm of macrophages. Furthermore, we found that interleukin-1β (IL-1β) induced by PA suppresses IFN-β response driven by the cGAS-STING-TBK1 pathway. Mechanistically, IL-1β decreased the production of cyclic GMP-AMP (cGAMP) by activating AKT kinase. cGAMP is necessarily sufficient to stimulate the transcription of IFN-β via the STING adaptor-TBK1 kinase-IRF3 transcription factor axis. Thus, our findings uncovered a novel module for PA intracellular survival involving IFN-β production restricted by IL-1β and provided a strong rationale for a potential clinical strategy against pulmonary PA infection patients. IMPORTANCE The link between innate immunity and intracellular Pseudomonas aeruginosa is unclear. Our studies illuminated the role of interferon-β (IFN-β) in remote intracellular PA infection. Furthermore, our experimental evidence also indicated that IL-1β is a negative regulator of IFN-β production and, in particular, P. aeruginosa infection. The inhibition of IFN-β may be used as a potential therapeutic method against pulmonary PA infection. American Society for Microbiology 2022-10-03 /pmc/articles/PMC9603546/ /pubmed/36190409 http://dx.doi.org/10.1128/spectrum.01550-22 Text en Copyright © 2022 Yang et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Yang, Ling
Zhang, Yu-Wei
Liu, Yang
Xie, Ying-Zhou
Weng, Dong
Ge, Bao-Xue
Liu, Hai-Peng
Xu, Jin-Fu
Pseudomonas aeruginosa Induces Interferon-β Production to Promote Intracellular Survival
title Pseudomonas aeruginosa Induces Interferon-β Production to Promote Intracellular Survival
title_full Pseudomonas aeruginosa Induces Interferon-β Production to Promote Intracellular Survival
title_fullStr Pseudomonas aeruginosa Induces Interferon-β Production to Promote Intracellular Survival
title_full_unstemmed Pseudomonas aeruginosa Induces Interferon-β Production to Promote Intracellular Survival
title_short Pseudomonas aeruginosa Induces Interferon-β Production to Promote Intracellular Survival
title_sort pseudomonas aeruginosa induces interferon-β production to promote intracellular survival
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603546/
https://www.ncbi.nlm.nih.gov/pubmed/36190409
http://dx.doi.org/10.1128/spectrum.01550-22
work_keys_str_mv AT yangling pseudomonasaeruginosainducesinterferonbproductiontopromoteintracellularsurvival
AT zhangyuwei pseudomonasaeruginosainducesinterferonbproductiontopromoteintracellularsurvival
AT liuyang pseudomonasaeruginosainducesinterferonbproductiontopromoteintracellularsurvival
AT xieyingzhou pseudomonasaeruginosainducesinterferonbproductiontopromoteintracellularsurvival
AT wengdong pseudomonasaeruginosainducesinterferonbproductiontopromoteintracellularsurvival
AT gebaoxue pseudomonasaeruginosainducesinterferonbproductiontopromoteintracellularsurvival
AT liuhaipeng pseudomonasaeruginosainducesinterferonbproductiontopromoteintracellularsurvival
AT xujinfu pseudomonasaeruginosainducesinterferonbproductiontopromoteintracellularsurvival