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Single cell transcriptomics of impact of HIV on latent TB infection in a rhesus macaque model of Mtb/SIV co-infection

ABSTRACT: HIV coinfection impairs Mtb-specific immunity resulting in reactivation of a latent TB infection (LTBI) in a subset of individuals. We performed Single cell RNA sequencing (scRNA-seq) on bronchalvolear lavage (BAL) samples collected at pre-determined time points from Mycobacterium tuberculosis (Mtb)/ Simian Immunodeficiency Virus (SIV) co-infected rhesus macaques. We identified a total of 14 clusters including monocytes, natural killer (NK) cells, T regs, central memory CD4+ T cells, B cells, club cells and neutrophils in the airways of Mtb/SIV co-infected rhesus macaques. Diminished expression of TH1 cell-specific transcription factors after SIV co-infection was not rescued despite effective cART. In contrast, SIV co-infection led to a reduction in the expression of immunoregulators in monocyte clusters; but increased expression of genes involved in interferon signaling, TH17 induction, T cell activation and tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS). Increased inflammation and migratory gene expression was observed in dendritic cells upon SIV co-infection. Overall, the lungs of SIV co-infected macaques with LTBI-like controlled, asymptomatic Mtb infection are characterized by the presence of chronic immune activation at the transcriptomic level, which can persist despite cART. Our work identifies key cell subsets, including novel ones, impacted by HIV coinfection of a latent TB infection in a biologically relevant animal model.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE254038 | GEO | 2026/06/01

REPOSITORIES: GEO

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