# Human airway microfold cells in mucosal immunity to bacterial pathogens

> **NIH NIH U01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $427,748

## Abstract

Project Summary/Abstract
The nasopharyngeal and respiratory mucosa represents a primary barrier to infection by inhaled organisms.
However, many pathogens have adapted and can disseminate beyond the oral and respiratory mucosa to
cause systemic disease. Such pathogens include Mycobacterium tuberculosis, Staphylococcus aureus,
Streptococcus pneumonia, and Bacillus anthracis. Together these pathogens account for millions of deaths
worldwide every year, and in particular, M. tuberculosis continues to be a devastating global pathogen, alone
causing two million deaths annually and latently infecting a third of the world’s population. Lining the respiratory
mucosa are specialized epithelial cells that function to transcytose mucosal antigens from the apical, mucosal
lumen 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 hypothesized that M. tuberculosis has evolved to penetrate the mucosa via M-cells, and our
preliminary data indicate that M. tuberculosis indeed utilizes M-cells to initiate disease. Blocking M-cell
development or secretion of an M. tuberculosis virulence factor prevents lymph node dissemination and
mortality from M. tuberculosis infection in mice. We will apply genetic, biochemical, immunologic and animal
approaches to determine the functional role of M-cells in mucosal and systemic immunity against respiratory
pathogens. Thus, in the proposed research we will (1) Characterize the transcytosis machinery leveraged by
bacteria to cross airway M-cells, (2) Assess the role of airway M-cells in inducing innate and adaptive immunity
in mice and (3) Determine the role of airway M-cells in the immune response using primary human tissues. The
proposed work is expected to identify how M-cells bind and transcytose M. tuberculosis and similar bacteria,
and the consequences of M-cell mediated transcytosis to innate and adaptive immune responses.

## Key facts

- **NIH application ID:** 9971432
- **Project number:** 5U01AI125939-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** MICHAEL SHILOH
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,748
- **Award type:** 5
- **Project period:** 2016-07-21 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971432

## Citation

> US National Institutes of Health, RePORTER application 9971432, Human airway microfold cells in mucosal immunity to bacterial pathogens (5U01AI125939-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9971432. Licensed CC0.

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