Immunopathogenesis of TB-HIV Co-Infection: Mechanisms of Dual Immune Suppression and Viral-Bacterial Synergy.

Authors

Maneesh Kumar, Ratul Bhowmik, Suman Kumar, Roshan Kamal Topno, Ganesh Chandra Sahoo, Shyam Kishor Kumar, Outi M H Salo-Ahen, Ashok Aspatwar

Published in

Virology. Volume 624. Pages 111054. Aug 18, 2026. Epub Aug 18, 2026.

Abstract

Human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (M. tuberculosis) co-infection represents one of the most devastating syndemics in global health, accounting for substantial morbidity and mortality worldwide. The interaction between these two pathogens is not merely additive but highly synergistic, driven by profound immune dysregulation. HIV-mediated depletion of CD4⁺ T cells facilitates tuberculosis (TB) progression, whereas TB-induced immune activation enhances HIV replication and accelerates disease progression. HIV preferentially infects CD4⁺ T cells and impairs the function of macrophages and dendritic cells, resulting in defective granuloma formation, impaired antigen presentation, and chronic systemic inflammation. Conversely, active TB promotes sustained production of cytokines and chemokines, creating a permissive environment for increased HIV transcription, viral dissemination, and maintenance of viral reservoirs. This review synthesizes current knowledge on the immunopathogenesis of TB-HIV co-infection, with particular emphasis on the mechanisms underlying dual immune suppression, including granuloma destabilization, macrophage dysfunction, impaired antigen presentation, immune exhaustion, cytokine imbalance, and disruption of mucosal and tissue immune homeostasis. We further examine how the bidirectional interplay between HIV and M. tuberculosis reshapes both innate and adaptive immune responses, contributing to atypical clinical manifestations, diagnostic challenges, immune reconstitution inflammatory syndrome (IRIS), and poor treatment outcomes. Finally, we discuss emerging host-directed and immunomodulatory therapeutic strategies, together with the growing role of systems biology and computational approaches in identifying immune correlates and predictive biomarkers. A deeper understanding of these interconnected mechanisms will be essential for developing integrated, personalized therapeutic strategies to improve clinical outcomes in individuals with TB-HIV co-infection.

PMID:
42679600
Bibliographic data and abstract were imported from PubMed on 02 Sep 2026.

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