Chlamydia psittaci inclusion membrane protein CPSIT_0842 induces macrophage apoptosis through MAPK/ERK-mediated autophagy.


Journal

The international journal of biochemistry & cell biology
ISSN: 1878-5875
Titre abrégé: Int J Biochem Cell Biol
Pays: Netherlands
ID NLM: 9508482

Informations de publication

Date de publication:
04 2023
Historique:
received: 01 06 2022
revised: 20 12 2022
accepted: 26 01 2023
pubmed: 31 1 2023
medline: 22 3 2023
entrez: 30 1 2023
Statut: ppublish

Résumé

Chlamydia psittaci is a multi-host zoonotic pathogen, which mainly infects poultry and inflicts an appreciable economic burden on the livestock farming industry. C. psittaci inclusion membrane proteins are uniquely positioned at the host-pathogen interface and are important virulence proteins. We have previously confirmed that Incs regulate host cell survival to help Chlamydia sp. evade host-cell-mediated defense mechanisms. However, the role of the Inc, CPSIT_0842, in the regulation of cell death following the establishment of persistent C. psittaci infection remains unknown. This study explored the effect of CPSIT_0842 on the crosstalk between the autophagic and apoptotic pathways in macrophages. Results showed that CPSIT_0842 initiated autophagy and blocked autophagic flux in human macrophages, as indicated by autophagy-related protein LC3-II, Beclin-1, and p62 upregulation, autophagosome accumulation, and lysosomal protein LAMP1 diminution. We also showed that the disruption of autophagic flux had a regulatory effect on CPSIT_0842-induced apoptosis. Moreover, the suppression of autophagy initiation by 3-methyladenine attenuated CPSIT_0842-induced apoptosis. By contrast, the induction of autophagic flux by rapamycin did not significantly affect CPSIT_0842-induced apoptosis. Taken together, these findings demonstrate that CPSIT_0842 induced macrophage apoptosis by initiating incomplete autophagy through the MAPK/ERK/mTOR signaling pathway, which may be instrumental to the ability of C. psittaci to evade the host innate immune response and establish persistent infection. The improved understanding of the autophagic and cell death pathways triggered upon bacterial inclusion will likely help in the development of novel treatment strategies for chlamydia infection.

Identifiants

pubmed: 36716815
pii: S1357-2725(23)00015-8
doi: 10.1016/j.biocel.2023.106376
pii:
doi:

Substances chimiques

Membrane Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

106376

Informations de copyright

Copyright © 2023. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declarations of interest None.

Auteurs

Yanru Huang (Y)

Institute of Pathogenic Biology, Hengyang Medical School, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, Hunan, China.

Sijia Li (S)

Institute of Pathogenic Biology, Hengyang Medical School, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, Hunan, China.

Siqin He (S)

Institute of Pathogenic Biology, Hengyang Medical School, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, Hunan, China.

Yumeng Li (Y)

Institute of Pathogenic Biology, Hengyang Medical School, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, Hunan, China; Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang 421000, Hunan, China.

Qingzhi He (Q)

School of Biotechnology, Guilin Medical University, Guilin 541199, China.

Yimou Wu (Y)

Institute of Pathogenic Biology, Hengyang Medical School, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, Hunan, China. Electronic address: yimouwu@sina.com.

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