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Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infection.

Authors :
Yu, Fengting
Ma, Chengjie
Jin, Xia
Zhao, Hongxin
Xiao, Jiang
Li, Li
Song, Shujing
Xie, Xiaohui
Yang, Siyuan
Tang, Yunxia
Wang, Linghang
Zhang, Fujie
Source :
BMC Infectious Diseases; 1/24/2024, Vol. 24 Issue 1, p1-11, 11p
Publication Year :
2024

Abstract

Background: In HIV-1 infection, more than 95% of CD4<superscript>+</superscript>T cells die of caspase-1 mediated pyroptosis. What governs the increased susceptibility of CD4<superscript>+</superscript>T cells to pyroptosis is poorly understood. Methods: Blood samples were obtained from 31 untreated HIV-infected patients (UNT), 29 antiretroviral therapy treated HIV-infected patients (ART), and 21 healthy control donors (HD). Plasma levels of IL-18 and IL-1β, caspase-1 expression, mitochondrial mass (MM) and mitochondrial fusion/fisson genes of CD4<superscript>+</superscript>T subsets were measured. Results: A significantly higher IL-18 level in plasma and MM level of CD4<superscript>+</superscript>T cells were found in HIV-infected patients (UNT and ART) compared to HD, and the MM<superscript>high</superscript> phenotype was manifested, related to increased caspase-1 expression. Moreover, the increased MM was more pronounced in the early differentiated and inactivated CD4<superscript>+</superscript>T cells. However, higher MM was not intrinsically linked to T cell differentiation disorder or excessive activation of the CD4<superscript>+</superscript>T cells. Mechanistically, the increased MM was significantly correlated with an elevated level of expression of the mitochondrial fusion gene mitofusin1. Conclusion: An increase in MM was associated with heightened sensitivity of CD4<superscript>+</superscript>T cells to pyroptosis, even in early differentiated and inactivated CD4<superscript>+</superscript>T cells, in patients with HIV-1 infection, regardless of whether patients were on antiretroviral therapy or not. These new revelations have uncovered a previously unappreciated challenge to immune reconstitution with antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14712334
Volume :
24
Issue :
1
Database :
Complementary Index
Journal :
BMC Infectious Diseases
Publication Type :
Academic Journal
Accession number :
175005240
Full Text :
https://doi.org/10.1186/s12879-023-08485-5