# Dynamics of tuberculosis immune response in peripartum HIV-infected and HIV-uninfected women

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $194,375

## Abstract

ABSTRACT
Tuberculosis (TB) is the leading infectious cause of death worldwide, and contributes to substantial morbidity
and mortality among HIV-infected peripartum women and their children. Risk of active TB appears to be
higher during pregnancy/postpartum, but it is not known whether pregnancy-associated immunologic changes
contribute to this increased susceptibility. Improved understanding of the host factors that influence M.
tuberculosis (Mtb) infection and TB disease severity is needed to improve TB treatments and vaccines. Multiple
lines of evidence indicate pregnancy diminishes T cell immunity to pathogens and may impair innate immune
recognition of Mtb. After Mtb infection, macrophages and dendritic cells initiate the immune response, leading to
mycobacterial killing, granuloma formation, and T cell activation. Our long-term goal is to determine the molecular
and cellular mechanisms that influence susceptibility to TB. Discovery of the immune changes that influence Mtb
pathogenesis in pregnancy may lead to improved public health efforts to reduce Mtb morbidity and transmission
in at-risk populations. The objective of this grant is to characterize the effect of pregnancy on innate and adaptive
immune responses to Mtb using stored samples that permit the study of immune responses pre-, during, and
post-pregnancy. The central hypothesis is that pregnancy dampens the innate immune response to Mtb in a
deleterious fashion, weakening Mtb-specific T cell responses and increasing TB susceptibility. The rationale is
that identification of factors that influence Mtb-specific innate and T cell immunity in a nuanced fashion provides
a novel path toward rational vaccine design and provides better understanding of high-risk populations. Our
specific aims will test the following hypotheses: 1) pregnancy diminishes the proportion of CD4+IFN+ T cells
and polyfunctional TH1 and CD8+T cells in pregnant women with latent Mtb infection; and 2) pregnancy impairs
the capacity of peripheral blood monocytes to induce proinflammatory cytokines to Mtb and permits increased
intracellular replication. This contribution is significant because it will establish the immune mechanisms that are
influenced by pregnancy in the context of HIV, using samples from pre- and post-pregnancy and from HIV-
uninfected women as a comparison; this proposal will lead to better understanding of the effects of pregnancy
on macrophage and T cell biology. The proposed work is innovative because we assembled a new collaborative
team with extensive experience in epidemiology and immunology to analyze banked samples with innovative
controls, in an understudied population (HIV-infected, pregnant women), utilizing cutting-edge statistical tools, to
measure innate immune and T cell responses. Insight into pregnancy as an immunomodulatory condition is
impactful because this approach may offer new targets for novel therapeutics and vaccines, and will provide
clinically relevant epidemiologic and ...

## Key facts

- **NIH application ID:** 9906951
- **Project number:** 5R21HD098746-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Sylvia LaCourse
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2019-04-04 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906951

## Citation

> US National Institutes of Health, RePORTER application 9906951, Dynamics of tuberculosis immune response in peripartum HIV-infected and HIV-uninfected women (5R21HD098746-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9906951. Licensed CC0.

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