# Host factors in shigellosis

> **NIH AI R01** · UNIVERSITY OF VIRGINIA · 2026 · $702,315

## Abstract

Abstract
The intestinal pathogen Shigella flexneri is the causative agent of bacillary dysentery and is responsible for
more than 250 million cases of dysentery annually, resulting in more than 200,000 deaths. The disease results
from epithelial cell infection in the colon, leading to mucosal ulceration, vascular lesions and massive immune
cell infiltration. Various animal models have been used to model various aspects of the disease, but none of
these models recapitulated the colonic symptoms of human shigellosis. We have recently shown that infant
rabbits experience all the symptoms of human shigellosis, including epithelial fenestration in the colon,
vascular lesions, immune cell infiltration, and bloody diarrhea. Here, we propose to use the infant rabbit model
of shigellosis to investigate the role of host factors in the disease and clarify aspects that are controversial in
the field. In Aim1, we will determine the route of intestinal cell infection in the colon. The prevalent view is that
S. flexneri invades the epithelium via M cells, a notion that was derived from studies conducted in the small
intestine of adult rabbits. Our preliminary data however suggest that in the colon, S. flexneri directly invade
epithelial cells. In Aim2, we will clarify the exact role of neutrophils in shigellosis. We will determine if they are
the cause of extensive damage inflicted to the colonic tissue, as previously suggested, or if they are indeed
beneficial and required for confining the infection process to the mucosa. In Aim3, we will determine the
mechanisms supporting S. flexneri interaction with macrophages and dendritic cells, and their role in regulating
the resolution of shigellosis.

## Key facts

- **NIH application ID:** 11233256
- **Project number:** 5R01AI179778-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** HERVE F AGAISSE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $702,315
- **Award type:** 5
- **Project period:** 2023-12-01T00:00:00 → 2028-10-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11233256

## Citation

> US National Institutes of Health, RePORTER application 11233256, Host factors in shigellosis (5R01AI179778-03). Retrieved via AI Analytics 2026-05-19 from https://api.ai-analytics.org/grant/nih/11233256. Licensed CC0.

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