Wednesday, August 20, 2025 8/20/2025

Single cell trancriptomics to identify LTBI reactivation markers in TB/HIV co-infection

Award Number: R21AI170148
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/18/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2026

Group Awards By:

View Award Description

Single cell trancriptomics to identify LTBI reactivation markers in TB/HIV co-infection - Project Summary The global control of tuberculosis (TB) is compounded by co-infection with Human Immunodeficiency Virus (HIV). Those infected with HIV are at high risk of reactivating latent TB infection (LTBI). Viral-induced chronic immune activation rather than mere depletion of CD4+ T cells correlates with LTBI reactivation due to SIV co-infection. Further, combinatorial antiretroviral therapy (cART) fails to restore T-effector functions and thus prevent LTBI reactivation in a nonhuman primate model of TB/SIV co-infection. Investigating the impact of cART on chronic immune activation in a relevant co-infected preclinical model at the single cell level will lead to the identification of key biomarkers predicting LTBI reactivation. We will synergize the research proposed here with a funded K01-award aims to collect cohesive data from archived control samples (uninfected, LTBI, SIV infected, Mtb/SIV co-infected but cART naïve; archived samples) and Mtb/SIV co-infected short-term, long-term cART treated (K-award) rhesus macaques. Based on our findings from the co-infection study, we hypothesize that while initiating cART at peak viremia in Mtb/SIV co- infection causes a significant decline in immune activation and macrophage turnover, it fails to rescue the skewed CD4+T effector memory responses leading to LTBI reactivation. Thus, in Aim 1, we will identify the specific lineage markers in the interplay between macrophages and CD4+ T cells that remain impaired despite cART in Mtb/SIV co-infected rhesus macaques. In Aim 2, we will investigate the earliest events of SIV-driven chronic immune activation and compare our findings to cART treated cohorts. For this, i) we will compare the activation status of plasmacytoid dendritic cells (pDCs) and NK cells in Mtb/SIV co-infection, ii) we will study the impact of cART on plasmacytoid dendritic cell (pDC)-driven Type-I Interferon (IFN) production and its impact on downstream effector responses compared to untreated controls. Overall, we will be able to determine if i) macrophage turnover interferes with CD4+ T cell restoration and function, ii) if cART effectively controls the earliest events of virus-driven immune activation by improving NK cell function and iii) the impact of cART on Type-I IFN response in driving the immune activation in Mtb/SIV co- infection. Studying the impact of cART on immune activation in Mtb/SIV co-infection is critical to identifying biomarkers for therapeutics and vaccine design to prevent LTBI reactivation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	000	2	7/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $387,333 )
2023	2023	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	000	2	7/14/2023	NON-COMPETING CONTINUATION	$387,333
														Subtotal = $387,333

Issue Date FY: 2022 ( Subtotal = $412,506 )
2022	2022	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	000	1	8/18/2022	NEW	$412,506
														Subtotal = $412,506

Grand Total All Awards = $799,839

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Single cell trancriptomics to identify LTBI reactivation markers in TB/HIV co-infection

Award Number: R21AI170148

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/18/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer