# Dissection of Shigella pathogenesis in vivo using a new oral infection mouse model

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $438,295

## Abstract

Project Summary/Abstract
Shigella species are highly infectious and important pathogens of humans. In 2016, there were an
estimated 269 million cases and 212,000 deaths due to Shigella. Humans are typically infected with
Shigella after oral ingestion of a minimal inoculum, consisting of as few as 10-100 bacteria. A major
roadblock in Shigella research is the lack of an in vivo oral infection mouse model that recapitulates key
aspects of human disease. Mice resist oral doses of Shigella as high as 100 million bacteria, but the reason
for this resistance remains poorly understood. In our preliminary data, we describe our discovery that the
reason mice are resistant to Shigella is because of a robust and mouse-specific innate immune
inflammasome response in intestinal epithelial cells. Mice lacking inflammasomes are thus susceptible to
oral Shigella infection and provide the first opportunity to use the full repertoire of mouse genetic and
immunological tools and methodologies to dissect Shigella pathogenesis in a physiological infection model.
Importantly, our data suggest that inflammasome-deficient mice are a highly relevant model because, in
humans, we find Shigella inhibits or evades the NAIP/NLRC4 inflammasome. We propose three Specific
Aims. In Aim 1, we will characterize innate immune and bacterial factors responsible for shigellosis in vivo.
In Aim 2, we will characterize the adaptive immune responses of mice to wild-type and mutant Shigella. In,
Aim 3, we will test the hypothesis that Shigella encodes effectors to inactivate the human NAIP/NLRC4
inflammasome. By exploiting the experimental tractability of our new model, we hope to identify the key
factors mediating immunity and disease during Shigella infection, thereby providing a foundation of
knowledge to inform the development of safer and more effective vaccines.

## Key facts

- **NIH application ID:** 10464909
- **Project number:** 5R01AI155634-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** RUSSELL E VANCE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $438,295
- **Award type:** 5
- **Project period:** 2020-09-22 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464909

## Citation

> US National Institutes of Health, RePORTER application 10464909, Dissection of Shigella pathogenesis in vivo using a new oral infection mouse model (5R01AI155634-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10464909. Licensed CC0.

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