# The role of colonic tuft cells in microbial detection and mucosal immunity

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $610,887

## Abstract

Project Summary
Parasitic worms constitute a major global public health burden, with approximately one-fifth of the
human population harboring one or more species within their gastrointestinal tract. We discovered
that rare chemosensory epithelial cells called tuft cells sense parasites and initiate a type 2
immune response in the small intestine. Subsequent investigations into tuft cells at other barrier
tissues throughout the body showed these cells respond to various microbial and environmental
triggers. However, despite the massive density of microbes in the colon, the activation of tuft cells
and their influence on type 2 immunity in the large intestine remains poorly understood. Several
studies demonstrated key differences between tuft cells in the small intestine and colon, including
distinct receptor profiles and divergent differentiation requirements. Recently, we found that
commensal tritrichomonad protists in the microbiome are far more diverse than previously
appreciated and stimulate colonic tuft cells and type 2 immunity independent of the tuft cell
agonist, succinate. In Aim 1, we will examine the impact of tritrichomonad-tuft cell interactions on
colonic immunity and determine the mechanisms colonic tuft cells use to initiate inflammation
within the large intestine. Aim 2 will identify the novel tuft cell receptor(s) activated by
tritrichomonads in the colon. Aim 3 will investigate the impact of colonic tuft cells on barrier
function, epithelial protein secretion, and mucosal resistance to enteric pathogens. The results of
this study will provide new insights into the microbial surveillance mechanisms of tuft cells in the
colon and their influence on mucosal immunity. This knowledge will also reveal the potential for
commensal protists to protect from enteric infections and provide a basis for using colonic tuft
cells to treat inflammatory disorders in the large intestine.

## Key facts

- **NIH application ID:** 10981281
- **Project number:** 1R01DK138076-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Michael R Howitt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $610,887
- **Award type:** 1
- **Project period:** 2024-07-05 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981281

## Citation

> US National Institutes of Health, RePORTER application 10981281, The role of colonic tuft cells in microbial detection and mucosal immunity (1R01DK138076-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10981281. Licensed CC0.

---

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