Mitochondrial Disturbance Related to Increased Caspase-1 of CD4T Cells in HIV-1 Infection

Overview

Journal BMC Infect Dis

Publisher Biomed Central

Specialty Infectious Diseases

Date 2024 Jan 24

PMID 38267841

Authors

Fengting Yu

Chengjie Ma

Xia Jin

Hongxin Zhao

Jiang Xiao

Li Li

Shujing Song

Xiaohui Xie

Siyuan Yang

Yunxia Tang

Linghang Wang

Fujie Zhang

Affiliations

Soon will be listed here.

Abstract

Background: In HIV-1 infection, more than 95% of CD4T cells die of caspase-1 mediated pyroptosis. What governs the increased susceptibility of CD4T 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 CD4T subsets were measured.

Results: A significantly higher IL-18 level in plasma and MM level of CD4T cells were found in HIV-infected patients (UNT and ART) compared to HD, and the MM phenotype was manifested, related to increased caspase-1 expression. Moreover, the increased MM was more pronounced in the early differentiated and inactivated CD4T cells. However, higher MM was not intrinsically linked to T cell differentiation disorder or excessive activation of the CD4T 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 CD4T cells to pyroptosis, even in early differentiated and inactivated CD4T 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.

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