# Cryptosporidiosis and Oral Tolerance

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2024 · $194,375

## Abstract

ABSTRACT
Cryptosporidiosis is an important cause of diarrheal disease in young children in the developing world where it
causes significant mortality and morbidity. Children that present with symptomatic disease are more likely to
suffer from malnutrition and lower height and weight per age, and these deficiencies persist for years after the
primary infection resolves. Surprisingly even asymptomatic cases can be associated with malnutrition and
failure to thrive for several years beyond the initial infection. These findings suggest that alterations in intestinal
function during the initial infection establish persistent enteropathy that stunts development. However, the
cellular and molecular mechanisms driving this clinical outcome remain unresolved. During early development
of the intestine, Goblet cells play a critical role in sampling of antigens from the gut lumen in a process that
generates peripheral T regulatory cells (pTreg), which suppress immune responses to dietary antigens and
commensals. This early process in shaping the mucosal immune system is critical to maintenance of oral
tolerance later in life. Our study examines the intriguing hypothesis that cryptosporidiosis in early life alters
responses to lumenal antigens by disrupting oral tolerance that normally develops during this time period. In
preliminary studies we have shown that neonatal mice, which are highly susceptible to C. parvum infection,
show defects in Goblet cell functions related to antigenic sampling. Furthermore we show that C. parvum
infected neonatal mice have reduced development of pTreg cells. We will explore the hypothesis that
cryptosporidiosis disrupts oral tolerance through two main aims: 1) determine the molecular mechanism for
disruption of antigen sampling by Goblet cells, 2) explore the consequence of disrupted pTreg development on
oral tolerance. These studies will explore how altered immune responses to dietary antigens or commensal
organisms drive inflammation that impairs gut function following enteric infection.

## Key facts

- **NIH application ID:** 10874696
- **Project number:** 5R21AI171858-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** L. David Sibley
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2023-06-23 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874696

## Citation

> US National Institutes of Health, RePORTER application 10874696, Cryptosporidiosis and Oral Tolerance (5R21AI171858-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10874696. Licensed CC0.

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