# Interaction of Mycobacterium tuberculosis with upper airway mucosal cells

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $707,176

## Abstract

Project Summary
The nasopharyngeal and respiratory mucosa represents a primary barrier to infection by inhaled organisms.
Indeed, the earliest contact point between the airway pathogen Mycobacterium tuberculosis and the human
body is the airway mucosa. As a result, M. tuberculosis has evolved to disseminate beyond the oral and
respiratory mucosa to cause systemic disease, thus accounting for its global impact on human morbidity and
mortality. Lining the airway mucosa are specialized epithelial cells that function to transcytose mucosal
antigens from the mucosal surface to the basolateral space. These cells, known as microfold or M cells, overlie
mucosal associated lymphatic tissue where macrophages and dendritic cells await to ingest and present
antigens to B-cells and T-cells. We previously demonstrated that M. tuberculosis penetrates the mucosa via M
cells by using a virulence factor called EsxA and a host receptor, scavenger receptor B1 (SR-B1). However, a
major gap in our understanding of the impact of this very early event on the interaction of M. tuberculosis with
the airway is that we do not fully understand M cell biology. Here, we will apply genetic, biochemical,
immunologic, transcriptomic and animal approaches to determine the functional role of M-cells in mucosal and
systemic immunity against M. tuberculosis. Thus, in the proposed research we will: (1) Determine the
transcriptional profiles and functions of novel genes of primary human and mouse airway M cells at a single
cell level under both homeostatic conditions and after experimental M. tuberculosis infection, (2) Identify and
study unique cell-cell interactions of M cells with their adjacent epithelial and immune cells, (3) Characterize
the mechanisms of binding and transcytosis of M. tuberculosis by airway M cells, (4) Determine the
immunologic impact of M. tuberculosis transcytosis across airway M cells. The proposed work is expected to
identify how M cells bind and transcytose M. tuberculosis and how this very early event in the life cycle of M.
tuberculosis dictates the immunologic outcome of infection.

## Key facts

- **NIH application ID:** 10947878
- **Project number:** 1R01AI184584-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** MICHAEL SHILOH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $707,176
- **Award type:** 1
- **Project period:** 2024-06-10 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10947878

## Citation

> US National Institutes of Health, RePORTER application 10947878, Interaction of Mycobacterium tuberculosis with upper airway mucosal cells (1R01AI184584-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10947878. Licensed CC0.

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