# Macrophage metabolism in diabetes and tuberculosis comorbidity

> **NIH NIH R21** · UNIV OF ARKANSAS FOR MED SCIS · 2023 · $244,734

## Abstract

Project Summary/Abstract
The increase in diabetes patients in countries where tuberculosis (TB) is also endemic has led to the re-emerging
importance of diabetes as a serious risk factor for TB. There is an urgent need to implement strategies for TB
prevention and control among the millions of diabetes patients exposed to Mycobacterium tuberculosis (Mtb),
the causative agent of TB. Although diabetes is known to modulate immune responses, most of the studies on
TB-diabetes comorbidity have been primarily focused on the altered functions of lymphocytes. Lung
macrophages are among the first host cells that respond to Mtb and are recognized as one of the most crucial
cell types in determining the consequences of disease. Our previous work has demonstrated that lung
macrophage metabolism plays a critical role in promoting or controlling the progression of TB. However, whether
the increased susceptibility to TB in diabetes is caused by altered metabolic activities in lung macrophages is
virtually unknown, thus representing a significant knowledge gap. The phenotype and functions of tissue-resident
macrophages are greatly influenced by the level of nutrients in their environmental niches. Given that diabetes
induces chronic hyperglycemia, a key factor that contributes to the development of TB in diabetic conditions, we
hypothesize that the altered metabolism in lung macrophages, due to the hyperglycemic environment, leads to
increased susceptibility to TB in diabetes. We will test this hypothesis with two aims: Aim 1. Determine the impact
of hyperglycemia on the metabolic status and permissiveness of lung AMs during Mtb infection. Aim 2.
Interrogate how hyperglycemia influences the heterogeneity of lung macrophages in TB. We will use multi-
disciplinary approaches, including metabolism, genomics and microbiology to interrogate the underlying
mechanism of TB-diabetes comorbidity from a completely novel perspective.

## Key facts

- **NIH application ID:** 10645801
- **Project number:** 1R21AI175738-01
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Lu Huang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $244,734
- **Award type:** 1
- **Project period:** 2023-08-21 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10645801

## Citation

> US National Institutes of Health, RePORTER application 10645801, Macrophage metabolism in diabetes and tuberculosis comorbidity (1R21AI175738-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10645801. Licensed CC0.

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