# The Role of SLAMF1 in TB Immunity

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2021 · $196,875

## Abstract

PROJECT SUMMARY
Mycobacterium tuberculosis (Mtb) is the leading cause of death worldwide from an infection. Mtb is able to evade
innate immune defenses by growing in macrophages. Most people develop robust CD4+ T cell responses to Mtb
infection, which is important for host defense; however, despite marked T cell responses, 5-10% of infected
individuals will develop active tuberculosis (TB). The rationale behind this proposal is that if we better understood
the basis of the partial protection conferred by CD4+ T cells, we could enhance those responses within the
context of therapeutics to promote sterilizing immunity and such responses might serve as correlates of
protection for vaccines. Since previous work showed that CD4+ T cells have to directly recognize antigen
presenting cells in order to promote Mtb control, we sought to identify non-soluble factors that mediate
macrophage-T cell interactions. We discovered that the cell surface receptor Signaling Lymphocyte Activating
Molecule (SLAM) family member (SLAM/SLAMF1/CD150) is induced more than 400-fold in Mtb-infected
macrophages in response to antigen specific CD4+ T cells. In addition, SLAMF1 was more highly expressed by
infected macrophages as compared to uninfected macrophages in the same well. In addition, SLAMF1 was
induced on T cells when they were incubated with infected macrophages. SLAMF1 signals through homotypic
interactions; SLAMF1-expressing cells stimulate other SLAMF1-expressing cells. Thus, SLAMF1 is poised to
mediate direct macrophage-T cell interactions and potentiate the antimicrobial activity of both cells. Previous
studies established that SLAMF1 functions as a costimulatory molecule in CD4+ T cells, while in macrophages
SLAMF1 activates the NADPH oxidase and lysosomal trafficking, antimicrobial responses that we previously
showed are impaired during Mtb infection. Remarkably, we found that SLAMF1-induction in macrophages and
T cells also correlates with protection in nonhuman primates vaccinated with IV BCG, which affords an
unprecedented level of protection. Here, we will test our hypothesis that SLAMF1 signaling between infected
macrophages and CD4+ T cells promotes control of Mtb, and that further enhancing SLAMF1 signaling boosts
host protection. We will examine Slamf1 expression and localization to determine whether it is present on the
cell surface, at the immunological synapse, in association with Mtb phagosomes, and regulated by Mtb infection
and antigen specific T cells. We will determine its expression profile in nonhuman primate granulomas. We will
establish whether SLAMF1 restricts intracellular growth of Mtb in human and murine macrophages and whether
SLAMF1 activation enhances intracellular Mtb control. Finally, we will evaluate the importance of SLAMF1 in
vivo. Thus, at the conclusion of this project, we will have established that SLAMF1 mediates macrophage- T
cells signaling to promote intracellular control of Mtb. Our discoveries will enable future studie...

## Key facts

- **NIH application ID:** 10172847
- **Project number:** 5R21AI155380-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** JENNIFER A PHILIPS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $196,875
- **Award type:** 5
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172847

## Citation

> US National Institutes of Health, RePORTER application 10172847, The Role of SLAMF1 in TB Immunity (5R21AI155380-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10172847. Licensed CC0.

---

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