# Myeloid-Derived Suppressor Cells in Tuberculosis Granuloma Structure and Function

> **NIH NIH R21** · TUFTS UNIVERSITY BOSTON · 2020 · $223,850

## Abstract

Project Summary
There is a critical need for identification of factors contributing to TB-HIV co-infection outcomes and to
prioritize new treatment modalities for treating drug-resistant TB in immune suppressed populations. Recently,
it has been suggested that pharmacologic modulation of myeloid-derived suppressor cells (MDSC) may be
an alternative to antimicrobial therapy for TB. MDSC are a transient immature myeloid cell population derived
from a common progenitor cell, that have been shown to block T cell-activation by recruiting T-regulatory
lymphocytes and inducing PD-1 expression on immune cells. In both cancer and chronic infectious diseases,
MDSC have been associated with immune-suppression and dampening of the host’s immune response locally
in tissue microenvironments, but the role of MDSC in Mycobacterium tuberculosis (Mtb) disease progression is
unclear. In order to determine if MDSC are a useful target for adjunctive therapy for TB disease in immune
suppressed populations, their role in TB disease needs to be elucidated. We hypothesize that MDSC
contribute to local immune suppression in the lung during TB infection by influencing spatial infiltrates of
immune cells and decreasing numbers and/or antimicrobial effectiveness of resident macrophage/monocyte
populations within the granuloma. Myeloid derived suppressor cells (MDSC) have been associated with immune-
suppression and dampening of the host’s immune response locally in tissue microenvironments, but the role of
MDSC in Mycobacterium tuberculosis (Mtb) disease progression is unclear. We propose to determine if MDSC
are a useful target for adjunctive therapy for TB disease by establishing numbers and localization patterns of
MDSC in both human and mouse Mtb infected lung using a novel imaging platform, tissue cyclic
immunofluorescence (t-CyCIF) to evaluate MDSC in the context of the granuloma. The long-term goal of our
research is to establish the extent to which MDSC function and trafficking can be modulated
pharmacologically to improve TB treatment outcomes. By determining the spatial co-localization of
MDSC with other immune cells in human TB granulomas and establishing immune correlates of MDSC
tissue localization with tuberculosis infection and control in Diversity Outbred (DO) mice we can evaluate
MDSC as targets for host-directed therapy in TB treatment. In summary, we will use novel methodology, t-
CyCIF, coupled with a mouse model of human genetic diversity, to generate new knowledge regarding the role
of MDSC in TB disease. Methods to alter the expansion and infiltration of MDSC may aid TB vaccine design and
immunotherapy to promote mycobacterial clearance in both HIV infected an uninfected patients.

## Key facts

- **NIH application ID:** 10082741
- **Project number:** 1R21AI155003-01
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Amanda Martinot
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $223,850
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10082741

## Citation

> US National Institutes of Health, RePORTER application 10082741, Myeloid-Derived Suppressor Cells in Tuberculosis Granuloma Structure and Function (1R21AI155003-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10082741. Licensed CC0.

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