Talaromyces marneffei activates the AIM2-caspase-1/-4-GSDMD axis to induce pyroptosis in hepatocytes

Creators

Jinhao He, Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University
Gang Wang, Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University
Hong Zhang, Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University
Jing Han, Guangxi Collaborative Innovation Center for Biomedicine, Life Science Institute, Guangxi Medical University
Tao Chen, Department of Infectious Diseases, Liuzhou People’s Hospital
Zhongsheng Jiang, Department of Infectious Diseases, Liuzhou People’s Hospital
Xu Li, Department of Infectious Diseases, Liuzhou People’s Hospital
Jingzhen Lai, Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University
Wudi Wei, Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University
Junjun Jiang, Guangxi Collaborative Innovation Center for Biomedicine, Life Science Institute, Guangxi Medical University
Jiaguang Hu, Department of Infectious Diseases, Liuzhou People’s Hospital
Chuanyi Ning, Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University
Li Ye, Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University
Zhen Li, Guangxi Collaborative Innovation Center for Biomedicine, Life Science Institute, Guangxi Medical University
Hao Liang, Guangxi Collaborative Innovation Center for Biomedicine, Life Science Institute, Guangxi Medical University
Peng Zhang, Department of Infectious Diseases, Liuzhou People’s Hospital

Description

Talaromyces marneffei tends to induce systemic infection in immunocompromised individuals, which is one of the causes of the high mortality. The underlying molecular mechanisms of T.marneffei-induced abnormal liver function are still poorly understood. In this study, we found that T.marneffei-infected patients could develop abnormal liver function, evidenced by reduced albumin and increased levels of aspartate aminotransferase (AST) and AST/alanine aminotransferase (ALT). T. marneffei-infected mice exhibited similar characteristics. In vitro investigations showed that T.marneffei induced the death of AML-12 cells. Furthermore, we determined that T.marneffei infection induced pyroptosis in hepatocytes of C57BL/6J mice and AML-12 cells, demonstrated by the increase of AIM2, caspase-1/-4, Gasdermin D(GSDMD) and pyroptosis-related cytokines in T.marneffei-infected mice/cells. Importantly, cell death was markedly suppressed in the presence of VX765 (an inhibitor of caspase-1/-4). Furthermore, in the presence of VX765, T.marneffei-induced pyroptosis was blocked. Nevertheless, necroptosis and apoptosis were also detected in infected animal model at 14 days post-infection. In conclusion, T.marneffei induces pyroptosis in hepatocytes through activation of the AIM2-caspase-1/-4-GSDMD axis, which may be an important cause of liver damage, and other death pathways including necroptosis and apoptosis may also be involved in the later stage of infection.

Publication Date

1-1-2022

Publisher

figshare Academic Research System

DOI

10.6084/m9.figshare.19941580.v1

Document Type

Data Set

Identifier

10.6084/m9.figshare.19941580.v1

Embargo Date

1-1-2022

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