# The role of the tuft cell inflammasome in infection

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $394,033

## Abstract

Project summary
The intestinal epithelium is exposed to different classes of pathogens and is not only instrumental as a first line
of defense against invasion of the host, but also signals to immune cells in the underlying lamina propria when
pathogens are detected. The NAIP/NLRC4 inflammasome has emerged as an important innate immune
sensor in intestinal epithelial cells (IECs) in bacterial gastrointestinal infection, leading to rapid extrusion of
infected cells and release of cytokines and eicosanoids upon pathogen recognition. The role of innate immune
sensing and the NAIP/NLRC4 inflammasome at the level of individual subtypes of IEC is not well understood.
Recently, we discovered that tuft cells uniquely among IECs release the eicosanoid prostaglandin D2 (PGD2)
after inflammasome activation. Tuft cells are a rare subtype of IECs primarily known for their role in anti-
parasitic immunity. The role of tuft cells during bacterial infection in general as well as the role of released
PGD2 in intestinal immunity is unclear.
Our preliminary data show that tuft cell inflammasome activation leads to increased tissue levels of IL-22, an
antibacterial cytokine that can be produced by TH17 cells or innate lymphoid cells (ILCs), and that tuft cell
inflammasome expression protects from small intestinal bacterial colonization. Based on our preliminary data
and published data on PGD2 receptor expression we propose a tuft cell- ILC3 communication axis via PGD2.
We hypothesize that tuft cells are central sentinels of infection status of the small intestine and capable of
shifting the polarization of the intestinal immune response.
We aim to define the pathway leading to IL-22 increase after tuft cell inflammasome activation using in vivo
models of tuft cell specific inflammasome activation and conditional epithelial PGD2 synthase and ILC3 PGD2
receptor deficiency. Further we will define the importance of tuft cell infection and inflammasome activation
during bacterial gastroenteritis, using a model of infection clearance with an attenuated strain of Salmonella
that does not lead to systemic infection. We will also explore the capacity of the tuft cell inflammasome to affect
an ongoing type 2 immune response during co-infection with a parasite, Nippostrongylus brasiliensis, and
Salmonella. These studies will greatly contribute to our understanding of epithelial cell type specific pathogen
sensing and the intestinal immune systems capacity to react to different types of infection.
This proposal brings together studies in the Rauch laboratory at Oregon Health and Science University and the
expertise of the Tait Wojno laboratory at the University of Washington. Unique expertise in the Tait Wojno
laboratory in the use of murine models of helminth infection will be leveraged to collaborate on exciting studies
that complement expertise in the Rauch laboratory in epithelial cell biology, inflammasome biology, and
intestinal bacterial infection.

## Key facts

- **NIH application ID:** 10418402
- **Project number:** 1R01AI167974-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Isabella Rauch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $394,033
- **Award type:** 1
- **Project period:** 2022-01-20 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418402

## Citation

> US National Institutes of Health, RePORTER application 10418402, The role of the tuft cell inflammasome in infection (1R01AI167974-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10418402. Licensed CC0.

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