# Describing the innate immune response of mycobacterium tuberculosis at a single-cell resolution

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $70,244

## Abstract

Project Summary
Mycobacterium tuberculosis (MTB) is responsible for more deaths than any other infectious disease in the world.
Despite decades of investigation, little is known about the early interactions of MTB and the innate immune
system. Previous investigations have relied on bulk tissue methods that are limited in resolution within a
physiologic in vivo model and require further investigations ex vivo. Our group has investigated the cellular
recruitment of innate immune cells using these methods. We have shown mononuclear phagocytes (MPs)
recruited during MTB infection are heterogeneous and dynamic through time. In early infection, preliminary
results demonstrate a differential cell type involvement and rate of MTB cell-to-cell transfer depending on the
bacterial strain. However, our results are limited by the ability to investigate mechanisms and resolution to
describe unique cellular subtypes. Single-cell RNA sequencing (scRNA-seq) is an increasingly utilized method
that provides detailed description of cell types and cellular alterations in disease models. In this application, we
propose utilizing scRNA-seq for the first time in MTB-infected mice. This technology will allow us to describe the
mononuclear phagocyte population involved in the early stages of MTB infection, and elucidate which cell types
are conducive or resistant to MTB growth. We will investigate changes in this population in the absence of T
cells and in the absence of a critical MTB virulence factor, ESX-1. In addition, we will describe the cellular
pathway of infection over time to elucidate cell-to-cell transfer in the presence and absence of T cells and ESX-
1. In this way, we can begin to understand both the role of the host and the bacteria in the early stages of
infection, and provide essential information for the development of an effective vaccine against infection via
intercepting MTB cellular transfer.

## Key facts

- **NIH application ID:** 10143583
- **Project number:** 1F32HL159403-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Beth S Zha
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,244
- **Award type:** 1
- **Project period:** 2021-05-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143583

## Citation

> US National Institutes of Health, RePORTER application 10143583, Describing the innate immune response of mycobacterium tuberculosis at a single-cell resolution (1F32HL159403-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10143583. Licensed CC0.

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