# Host Determinants of Tuberculosis Susceptibility

> **NIH NIH P01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $477,037

## Abstract

Project 1: Host Determinants of TB Susceptility
Abstract: The outcomes of Mycobacterium tuberculosis (Mtb) infections are extremely
diverse. Many infected individuals show no signs of disease. Among those that do
become ill, the timing, location, and severity of pathology are remarkably variable.
Genetic diversity in the host population is a major contributor to this variability, but the
responsible alleles and mechanisms are poorly defined and have been difficult to
address experimentally. In this project, we approach this inherently complex problem by
modeling host diversity using a highly genetically diverse, but precisely genetically
defined, panel of recombinant inbred mice known as the Collaborative Cross. The
unique structure of this population allows the sequential evaluation of variable traits that
reflect distinct aspects of pathogenesis. We took advantage of this iterative-phenotyping
strategy to dissect the genetic basis of TB susceptibility at multiple levels. These prior
studies implicated Kit Ligand (KitL) variation as an important determinant of TB disease
in mice and humans, suggested that genetic interactions between pathogen and host
are a sensitive metric for detecting new genes that alter disease progression, and
highlighted the power of using ex vivo systems to dissect the interaction between Mtb
and the macrophage. In the proposed project, we will continue to pursue these
strategies to:
Aim 1: Investigate the mechanism of KitL-linked susceptibility to TB disease in
mice and humans.
Aim 2: Use combinatorial mouse and bacterial genetics to dissect host-pathogen
genetic interactions.
Aim 3: Exploit the CC panel to dissect the Mtb-macrophage interaction.
In combination, these new resources and approaches promise to provide fundamentally
new insight into the role of host and bacterial genetic variation on the outcome of Mtb
infection.
!

## Key facts

- **NIH application ID:** 10219087
- **Project number:** 5P01AI132130-05
- **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:** 2021
- **Award amount:** $477,037
- **Award type:** 5
- **Project period:** 2017-08-05 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219087

## Citation

> US National Institutes of Health, RePORTER application 10219087, Host Determinants of Tuberculosis Susceptibility (5P01AI132130-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10219087. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*