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

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.