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

Yanru Huang; Sijia Li; Siqin He; Yumeng Li; Qingzhi He; Yimou Wu

doi:10.1016/j.biocel.2023.106376

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

Int J Biochem Cell Biol. 2023 Apr:157:106376. doi: 10.1016/j.biocel.2023.106376. Epub 2023 Jan 28.

Authors

Yanru Huang¹, Sijia Li¹, Siqin He¹, Yumeng Li², Qingzhi He³, Yimou Wu⁴

Affiliations

¹ 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.
² 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.
³ School of Biotechnology, Guilin Medical University, Guilin 541199, China.
⁴ 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.

PMID: 36716815
DOI: 10.1016/j.biocel.2023.106376

Abstract

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.

Keywords: Apoptosis; CPSIT-0842; Chlamydia psittaci; Incomplete autophagy; MAPK/ERK pathway.

Publication types

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

MeSH terms

Apoptosis
Autophagy
Chlamydophila psittaci* / physiology
Humans
Membrane Proteins
Psittacosis* / metabolism
Psittacosis* / microbiology

Substances

Membrane Proteins