Abstract
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
Samantha Cronin, Jennifer Simpson, Andrea Pereyra-Casanova, Yuchen Li, Josefina Marín-Rojas, Freja A. Warner van Dijk, Katie Fisher, Daniel J. Buffa, Hafsa Rana, Zoï Vahlas, Joaquina Barros, Mariano Maio, Thomas R. O'Neil, Kirstie M. Bertram, Eunok Lee, Najla Nasr, Andrew N. Harman, Gabriela Turk, Maria Florencia Quiroga, Anthony D. Kelleher, Christel Vérollet, Luciana Balboa, Sarah Palmer, Gabriel Duette
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