# Epithelial intrinsic inflammasomes direct host defense against gut microbes

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2022 · $83,374

## Abstract

PROJECT SUMMARY
Enteric infections and their associated sequelae, including pain, nausea, inflammation and diarrhea, are major
causes of morbidity and mortality worldwide, particularly in children. Being at the frontline of intestinal host
defense, intestinal epithelial cells (IECs) are the frequent target of enteric pathogens. It is generally believed
that during enteric infections, the gut epithelium and overlying mucus layer, which are at the forefront of the
host-microbial interface, primarily provide a physical barrier against invading pathogens, whereas any innate
immune response that occurs within the intestinal mucosa is largely driven by the immune/inflammatory cells
resident in the lamina propria. In contrast, recent studies, including our own, ascribe an unprecedented role for
IECs as important players in gut innate immune responses. Together, these studies unequivocally showed that
canonical and non-canonical inflammasomes in IECs promote host defense and inflammatory responses at
early stages of infection by the model enteric pathogen, Salmonella enterica serovar Typhimurium. The
primary objective of this application is to define the contribution of IEC inflammasomes to antimicrobial host
defenses in the gut. Our general hypothesis is that IEC intrinsic inflammasomes coordinate several protective
and anti-microbial pathways at the gut mucosal surface. Two integrated specific aims are proposed to test this
hypothesis. First, we will delineate the protective role of IEC inflammasomes against enteric pathogens in vitro
and in vivo, and assess the regulation and temporal contribution of IEC canonical and non-canonical
inflammasomes during infection. Second, we will elucidate goblet cell-specific inflammasome-dependent
defense responses. Completion of this proposal will close a significant knowledge gap regarding the impact of
epithelium-intrinsic inflammasomes on intestinal antimicrobial defense, homeostasis and disease development.

## Key facts

- **NIH application ID:** 10428520
- **Project number:** 5R01AI134766-05
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Leigh Knodler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $83,374
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428520

## Citation

> US National Institutes of Health, RePORTER application 10428520, Epithelial intrinsic inflammasomes direct host defense against gut microbes (5R01AI134766-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10428520. Licensed CC0.

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