Exploring the mechanism of HIV infection on T lymphocyte mitochondrial damage based on MAPK pathway.
- Author:
Yong DENG
1
;
Cheng CHEN
2
,
3
;
Zhong CHEN
1
;
Gang XIAO
1
;
Guoqiang ZHOU
1
;
Fang ZHENG
1
;
Ning WANG
1
Author Information
1. Department of Infection and Immunology, Changsha First Hospital, Changsha 410005, China.
2. Tuberculosis Department of Changsha First Hospital, Changsha 410005, China. *Corresponding author, E-mail: qiaodi760@
3. com.
- Publication Type:Journal Article
- MeSH:
Humans;
HIV Infections/immunology*;
Male;
Mitochondria/drug effects*;
Female;
CD4-Positive T-Lymphocytes/metabolism*;
Adult;
Middle Aged;
MAP Kinase Signaling System/drug effects*;
Pyridines/pharmacology*;
Imidazoles/pharmacology*;
Leukocytes, Mononuclear/immunology*
- From:
Chinese Journal of Cellular and Molecular Immunology
2024;40(12):1096-1103
- CountryChina
- Language:Chinese
-
Abstract:
Objective To clarify the mechanism that HIV infection mediates mitochondrial damage of CD4+ T lymphocytes (CD4+ T cells) through mitogen-activated protein kinase (MAPK) pathway. Methods From October 1st, 2022 to March 31st, 2023, 47 HIV-infected people who received antiretroviral therapy (ART) for 4 years were recruited, including 22 immune non-responders (INR) and 25 responders (IR); and 26 sex and age-matched control participants (HC) who were negative for HCV, HBV, and HIV infections. The immune parameters were analyzed by flow cytometry. Finally, peripheral blood mononuclear cells (PBMCs) from HC or HIV patients were treated with MAPK pathway inhibitor SB203580, and the changes of mitochondrial function of CD4+ T cells were observed. Results Compared with HC group, the proportion of CD4+ T cells in PBMCs in INR group and IR group was significantly lower, and the proportion of CD4+ T cells in PBMCs in INR group was significantly lower than that in IR group. In addition, the proportion of naive (CD45RA+CD27+)T cells in PBMCs in INR group was significantly lower than that in HC group and IR group. Compared with HC group and IR group, the proportions of CD4+PD-1+, CD4+Av+ and CD4+MO+ in PBMCs in INR group and the proportions of CD45RA+CD27+PD-1+, CD45RA+CD27+Av+, CD45RA+CD27+MO+ in CD4+ T cell subsets increased significant. Compared with HC-con group, the basal respiration, maximal respiration and adenosine triphosphate(ATP) production of CD4+ T cells in HIV-con group decreased significantly, and JC-1 (green/red) in CD4+ T cells increased significantly. Compared with HIV-con group, the basal respiration, maximal respiration, ATP production and respiratory potential of CD4+ T cells in HIV-SB203580 group increased significantly, and the JC-1 (green/red) in CD4+ T cells decreased significantly. Conclusion Abnormal activation of the MAPK signaling pathway is observed in HIV patients receiving ART treatment, especially in CD4+ T cells of INR patients, which may lead to impaired mitochondrial function and abnormal CD4+ T cell homeostasis.
