# Innate immune response of LTBI+HIV+ children

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH CTR AT TYLER · 2022 · $695,140

## Abstract

Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and causes almost 1.3 million
deaths per year, including 100, 000 children. Approximately 90% of infected persons have latent tuberculosis
infection (LTBI), have protective immunity and remain well, but 10% develop primary tuberculosis (TB) soon
after infection or reactivation TB many years later. Children are more susceptible to TB infection, due to an
immature immune system. HIV infection in children markedly increases susceptibility to TB, and HIV-infected
persons with LTBI have an 800-fold greater risk of developing active TB (www.cdc.gov/tb/). TB is the leading
cause of death in HIV-infected persons and more than half a million coinfected people die annually. To develop
adequate prophylaxis or therapy, it is important to understand immune responses to Mtb. Identification of HIV+
children with LTBI who are at greatly increased risk for development of TB would allow treating only high-risk
children, facilitating completion of therapy for LTBI and preventing future development of TB. To identify these
children, it is important to pinpoint the nature of the defective immune responses that permit development of
active TB in HIV+LTBI+ pediatric patients.
 Over the past 18 years, we have published a series of articles demonstrating that human NK cells have
the potential to contribute to both innate and adaptive immune responses to Mtb. Our recently published
studies demonstrate that memory-like NK cells contribute to vaccine-induced protective immunity against Mtb
and IL-21 is required for expansion of memory-like NK cells in both humans and mice. Based on our
published studies, we hypothesize that HIV-LTBI+ children household contacts have defective
memory-like NK cell expansion compared to HIV-LTBI+ adult household contacts and these defects are
more severe in HIV+ LTBI+ children. The proposed studies in the current application will be performed in
India as a part of RePORT-India consortium. This study will leverage the large Indo-US investment and TB/HIV
research consortium of RePORT-India which has developed cohorts of TB cases and household contacts in
India and has paired Indian investigators with US investigators at 6 sites. Already collected samples will be
used for the proposed studies in aim 1. Our specific aims are: 1. Determine Mtb specific memory-like NK cell
responses of children in a large group of household contacts of TB patients. 2.Compare the memory-like NK
cell responses of HIV+ and HIV- children with LTBI. 3. Determine whether KIR haplotypes and HLA
polymorphism is associated with expansion of memory-like NK cells in children.

## Key facts

- **NIH application ID:** 10470320
- **Project number:** 5R01AI142672-03
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH CTR AT TYLER
- **Principal Investigator:** Ramakrishna Vankayalapati
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $695,140
- **Award type:** 5
- **Project period:** 2020-09-14 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470320

## Citation

> US National Institutes of Health, RePORTER application 10470320, Innate immune response of LTBI+HIV+ children (5R01AI142672-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10470320. Licensed CC0.

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