Faculty, Staff and Student Publications
Language
English
Publication Date
8-21-2026
Journal
iScience
DOI
10.1016/j.isci.2026.116944
PMID
42565131
PMCID
PMC13446293
PubMedCentral® Posted Date
7-27-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Using single-cell transcriptomics of bronchoalveolar lavage cells from Mtb/SIV co-infected rhesus macaques on cART, we reveal profound immune dysregulation during early SIV co-infection of latent tuberculosis. SIV induces a sharp decline in CD4+ T cells, NK, and NKT cells, with incomplete recovery of Mtb-specific TH1 effector responses despite viral suppression. Instead, a persistent TH17-skewed environment emerges, alongside sustained myeloid inflammation driven by Type I interferon signaling and pro-inflammatory regulators such as KLF6 and NFKB1. Ligand-receptor network analyses demonstrate expanded CD4+ T cell-macrophage crosstalk and loss of immune homeostasis that cART fails to fully restore. These findings expose how SIV remodels the pulmonary immune landscape to impair protective immunity against Mtb, providing a transcriptomic framework to explain TB reactivation in HIV infection. Our work highlights the urgent need for adjunctive immunotherapies to complement cART, aiming to rebalance immune responses and improve TB control in co-infected individuals.
Keywords
scRNA-seq, LTBI, HIV, NHP, Type I IFN, TB/SIV
Published Open-Access
yes
Recommended Citation
Sharan, Riti; Zou, Yi; Lai, Zhao; et al., "Early Immune Dysregulation in Mtb/Siv Co-infection Resists cART Treatment at the Single-Cell Level" (2026). Faculty, Staff and Student Publications. 1476.
https://digitalcommons.library.tmc.edu/uthsph_docs/1476
Graphical Abstract