Single cell transcriptomics of impact of HIV on latent TB infection in a rhesus macaque model of Mtb/SIV co-infection
Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B654
Abstract ID: 4359
Presenting Author:
Riti Sharan , Assistant Professor at Texas Biomed. Res. Inst.
Abstract:
HIV coinfection impairs Mtb-specific immunity resulting in reactivation of a latent TB infection (LTBI). We applied scRNA-seq to BAL samples from Mtb/SIV co-infected, cART treated rhesus macaques at key time-points to decipher cellular variables associated with LTBI reactivation. We have previously shown that reactivation of LTBI is governed by the early events post SIV coinfection in the RM model and that timing of cART is critical in mitigating chronic immune activation. We identified 14 clusters categorized as lymphoid, myeloid and novel subsets. SIV co-infection diminished i) expression of CD4 and TH1- response associated genes in lymphoid clusters, ii) reduced innate immune regulation gene expression and ii) increased interferon signaling and inflammation in innate clusters. Paracrine analysis showed SIV co-infection disrupted crosstalk between different innate immune cell subsets in pulmonary compartment in LTBI as early as within first couple of weeks. In conclusion, we report here transcriptomic changes induced by SIV co-infection of LTBI in both, innate and adaptive immune cell subsets. This is among the first study to investigate the impact of SIV co-infection on LTBI in a biologically relevant animal model at the single cell level. The data from this study will be critical for development of an immune-based intervention along with cART and anti-TB therapy to control dysregulated immune responses generated during early events of HIV co-infection of LTBI.
Single cell transcriptomics of impact of HIV on latent TB infection in a rhesus macaque model of Mtb/SIV co-infection
Category
Poster and Podium (Block Symposium)