The pleural tuberculosis-associated microenvironment promotes HIV-1 persistence by impairing CD8+ T cell-mediated viral control
Mycobacteriumtuberculosis (Mtb), the causative agent of tuberculosis (TB), is the most common coinfection in people living with HIV-1 (PLWH). This coinfection is associated with accelerated HIV-1 disease progression and reduced survival. However, the immunological and virological mechanisms driving this progression are not completely understood. To address this knowledge gap, using pleural effusion samples from PLWH and TB, we investigated how the HIV-1 genetic landscape and the anti-HIV-1 immune response are impacted by a TB-associated microenvironment. Our results revealed an enrichment of genetically intact HIV-1 and impaired CD8+ T cell-mediated antiviral response at this site of HIV-1/Mtb coinfection. Moreover, efficient CD8+ T cell activation was inhibited by lipids present in the TB-associated pleural effusion. These findings indicate that this immune microenvironment induced by TB promotes the persistence of cells infected with replication-competent HIV-1 by creating a niche of reduced antiviral immune pressure, potentially contributing to the worsened clinical outcomes observed in PLWH and TB.
Authors
- Joaquina Barros
- María Florencia Quiroga (ORCID: https://orcid.org/0000-0002-0956-5492)
- Zoï Vahlas (ORCID: https://orcid.org/0000-0003-2115-9312)
- Samantha Cronin (ORCID: https://orcid.org/0000-0002-7406-4870)
- Luciana Balboa (ORCID: https://orcid.org/0000-0001-7045-3572)
- Gabriel Duette (ORCID: https://orcid.org/0000-0002-0295-8998)
- Josefina Marín-Rojas (ORCID: https://orcid.org/0000-0002-0347-8291)
- Andrew N. Harman (ORCID: https://orcid.org/0000-0003-1535-1279)
- Katie Fisher (ORCID: https://orcid.org/0000-0002-8732-706X)
- Freja A. Warner van Dijk
- Mariano Maio
- Anthony Dominic Kelleher (ORCID: https://orcid.org/0000-0002-0009-3337)
- D Buffa (ORCID: https://orcid.org/0009-0006-2503-5367)
- Najla Nasr (ORCID: https://orcid.org/0000-0001-6249-9204)
- Eunok Lee (ORCID: https://orcid.org/0000-0002-5528-3859)
- Sarah Palmer
- Andrea Pereyra-Casanova
- Gabriela Turk
- Thomas R. O’Neil
- Christel Vérollet
- Hafsa Rana
- Yuchen Li
- Kirstie M. Bertram
- Jennifer Simpson
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Universidad de Buenos Aires (AR)
- UNSW Sydney (AU)
- Institut de Pharmacologie et de Biologie Structurale (FR)
- Westmead Institute for Medical Research (AU)
Publication Details
- Journal
- JCI Insight
- Published
- 2026-08-20
- DOI
- https://doi.org/10.1172/jci.insight.201268
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- amfAR, The Foundation for AIDS Research
- Styrelsen för Internationellt Utvecklingssamarbete
- Delaney AIDS Research Enterprise
- Sidaction
- David and Elaine Potter Foundation
- Australian Government
- Cancer Institute NSW
- University of Sydney
- Université de Toulouse
- Centre National de la Recherche Scientifique
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council
- Sydney Medical School
- Sydney Medical School Foundation