# Impact of tuberculosis on the development and function of the immune system in SIV-infected infants

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $466,181

## Abstract

PROJECT SUMMARY/ABSTRACT:
Tuberculosis (TB) is the leading cause of death in Human immunodeficiency virus/acquired immune deficiency
syndrome (HIV/AIDS) patients worldwide, and this is particularly true for infants. Although studies have
disclosed some aspects of pathological changes in HIV/Mtb co-infected adults, very little is known about the
pathogenesis and efficacy of therapeutic strategies in HIV-associated Mtb infection in infants, who possess a
developing immune system that increases their vulnerability to certain infectious diseases. Recent advances in
understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on
precursor frequencies of lymphocytes, antigenic dose, and mode of exposure. Clinical course of pediatric HIV
has revealed perinatally acquired HIV infection occurs during a critical window of immune development, and
HIV’s perturbation of this dynamic process may account for the striking age-dependent differences in HIV
disease progression. TB in young children is often imperceptible and can rapidly progress to active disease,
but the effects of Mtb on the developing immune system of infants is essentially unknown. Therefore, a better
understanding of the immunopathogenesis of HIV-associated Mtb infection in pediatric hosts is essential to
provide appropriate interventions, which can reduce risk of morbidity and mortality in infants co-infected with
HIV and Mtb. We have been using nonhuman primate models to study neonatal immunology and have shown
the neonatal immune system is highly compartmentalized, with a much more competent mucosal immune
system than the systemic system at birth, and pediatric SIV infection results in impaired development and
function of the neonatal mucosal and systemic immune systems. This proposal is designed to determine the
immunological changes induced by SIV infection that contributes to the increased severity of Mtb in infants,
and the effects of early antiretroviral therapy (ART) and immunotherapy (IDO-inhibitor treatment) on both
infections by comparing viral/bacterial burdens, innate, adaptive, and pathogen specific cellular and humoral
immune responses, pulmonary pathology, latency, reservoirs, and disease progression. The objectives of our
studies are to: a) characterize the effects of Mtb on the development and maturation of systemic and mucosal
immune systems in infant macaques that with or without immunotherapy; b) compare immune responses and
pathology in SIV/Mtb co-infected infant macaques; and c) determine whether early initiation of ART with
subsequent immunotherapy reduces morbidity and mortality among HIV-associated Mtb infection in infants. By
using a comprehensive and multipronged approach to define the impacts of Mtb infection on the development
and function of the immune system, and identifying mechanisms underlying restoration of Mtb-specific immune
function in SIV-infected infants, our studies will advance our understandings of the immunopath...

## Key facts

- **NIH application ID:** 10444441
- **Project number:** 3R01HD099857-03S1
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Deepak Kaushal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,181
- **Award type:** 3
- **Project period:** 2021-09-17 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444441

## Citation

> US National Institutes of Health, RePORTER application 10444441, Impact of tuberculosis on the development and function of the immune system in SIV-infected infants (3R01HD099857-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10444441. Licensed CC0.

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