# Project 1 Immunometabolic Determinants of Susceptibility

> **NIH NIH P01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $870,530

## Abstract

Project 1: Immunometabolic determinants of host susceptibility (Project Leader: Sassetti).
ABSTRACT:
Mycobacterium tuberculosis (Mtb) infection in different individuals, or even in different
anatomical sites in the same individual, progresses along a variety of trajectories producing a
wide spectrum of clinical outcomes – from asymptomatic control to progressive disease. While
many immunological mechanisms necessary for protective immunity have been identified, and
are common between humans and small animal models, the basis for the variable expression of
these defenses and the consequent diversity in outcome remains unclear. We have identified
an immuometabolic axis that controls the ability of the macrophage to integrate proinflammatory
and regulatory signals and influences Mtb infection outcome. In this Project, we will investigate
the mechanisms linking mitochondrial function, the unfolded protein response, and the
macrophage’s response to Mtb infection in cellular models, in intact animal models, and in
multiple human cohorts. The ultimate goals of the project are: (1) to understand the mechanistic
basis for variable immune response to Mtb infection, (2) to identify new and mechanistically-
informative immunometabolic markers of disease progression, and (3) to test the efficacy of
candidate immunotherapies in promoting protective immunity.

## Key facts

- **NIH application ID:** 10861329
- **Project number:** 1P01AI181898-01
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** CHRISTOPHER M SASSETTI
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $870,530
- **Award type:** 1
- **Project period:** 2024-08-20 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10861329

## Citation

> US National Institutes of Health, RePORTER application 10861329, Project 1 Immunometabolic Determinants of Susceptibility (1P01AI181898-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10861329. Licensed CC0.

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