HIV-induced autophagy suppression in tuberculosis pathogenesis: from mechanisms to therapeutic implications
- 1Biobank, Clinical Research Center, Chongqing Public Health Medical Center
- 2Department of Information, Chongqing Public Health Medical Center
- 3Department of Pharmacy, Chongqing Yubei People’s Hospital
Abstract
Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLWH) despite effective antiretroviral therapy (ART), with HIV infection increasing the risk of active TB by 16 to 27-fold. Even among virologically suppressed individuals on ART, the risk remains 4 to 7-fold higher than in HIV-negative populations, indicating that mechanisms beyond CD4+ T-cell depletion contribute to persistent TB susceptibility. Autophagy is a conserved lysosomal degradation pathway essential for intracellular pathogen clearance and immune regulation, and its dysregulation has emerged as a critical determinant of host-pathogen interactions in HIV/TB co-infection. In this review, we synthesize current evidence suggesting that HIV profoundly suppresses autophagy in key immune cells through the concerted actions of viral proteins, including Nef, Tat, and Env, through the off-target effects of ART drugs. This inhibition may disrupt macrophage antimicrobial functions, including phagosome maturation, xenophagy, and LC3-associated phagocytosis, while also impairing antigen presentation in dendritic cells. These defects may compromise communication between immune cells, attenuate T-cell responses, and create a permissive intracellular niche for Mycobacterium tuberculosis (Mtb) survival and proliferation. We propose an integrated mechanistic framework linking HIV-driven autophagy suppression to enhanced TB susceptibility, highlighting the synergistic interplay between HIV proteins and Mtb evasion strategies. By elucidating these molecular connections, we identify autophagy as a promising therapeutic target and highlight autophagy-directed host-directed therapies as a potential strategy to reduce the persistent TB burden in PLWH and advance toward a cure for both infections.
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BibTeX
@article{xia2026hivinduced,
title = {{HIV-induced autophagy suppression in tuberculosis pathogenesis: from mechanisms to therapeutic implications}},
author = {Chao Xia and Xiaobo Fan and Fang Cheng and Sen Yang and Xue Zhang and Yemiao Chen},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1990644},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1990644/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - HIV-induced autophagy suppression in tuberculosis pathogenesis: from mechanisms to therapeutic implications
AU - Chao Xia
AU - Xiaobo Fan
AU - Fang Cheng
AU - Sen Yang
AU - Xue Zhang
AU - Yemiao Chen
PY - 2026
DA - 2026/10/29
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1990644
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1990644/full
AB - Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLWH) despite effective antiretroviral therapy (ART), with HIV infection increasing the risk of active TB by 16 to 27-fold. Even among virologically suppressed individuals on ART, the risk remains 4 to 7-fold higher than in HIV-negative populations, indicating that mechanisms beyond CD4+ T-cell depletion contribute to persistent TB susceptibility. Autophagy is a conserved lysosomal degradation pathway essential for intracellular pathogen clearance and immune regulation, and its dysregulation has emerged as a critical determinant of host-pathogen interactions in HIV/TB co-infection. In this review, we synthesize current evidence suggesting that HIV profoundly suppresses autophagy in key immune cells through the concerted actions of viral proteins, including Nef, Tat, and Env, through the off-target effects of ART drugs. This inhibition may disrupt macrophage antimicrobial functions, including phagosome maturation, xenophagy, and LC3-associated phagocytosis, while also impairing antigen presentation in dendritic cells. These defects may compromise communication between immune cells, attenuate T-cell responses, and create a permissive intracellular niche for Mycobacterium tuberculosis (Mtb) survival and proliferation. We propose an integrated mechanistic framework linking HIV-driven autophagy suppression to enhanced TB susceptibility, highlighting the synergistic interplay between HIV proteins and Mtb evasion strategies. By elucidating these molecular connections, we identify autophagy as a promising therapeutic target and highlight autophagy-directed host-directed therapies as a potential strategy to reduce the persistent TB burden in PLWH and advance toward a cure for both infections.
SN - 1664-3224
ER -