# Role of Intestinal Parasites on Regulating Immune Responses to Gut Antigens

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $631,050

## Abstract

PROJECT SUMMARY/ABSTRACT
Gastrointestinal parasitic infection is a widespread global health problem and can be a cause of significant
morbidity. Nevertheless, there is limited information on how T cells respond to these parasites. In some cases,
despite a robust T cell effector response to the parasite, tolerance to food antigens is maintained or enhanced.
This has led to the notion that chronic parasitic infection could explain in part the hygiene hypothesis, which
states that elimination of colonization or reduction of recurrent infections due to sanitation and pest control
increases the risk of allergic and autoimmune diseases. We aim to understand how intestinal parasites induce
effector T cell responses to parasitic antigens, and yet facilitate tolerance to food antigens present in the
intestine. We will study two parasites that induce opposite T cell effector responses in mice. We will use a
newly identified strain of Cryptosporidium tyzzeri, a commensal protozoan that induces a Th1 response, and H.
polygyrus, a helminth that induces a Th2 response. The rationale for using parasites which elicit disparate T
helper responses is to uncover potentially convergent mechanisms that may underly prevention of
immunopathology during anti-parasitic responses and maintenance of tolerance to innocuous food antigens. In
each infection, we will use TCR repertoire analysis to identify parasite-specific TCRs expressed by CD4+ T
cells. This approach will allow us, for the first time, to precisely track the fate of such parasite-reactive T cells
during these infections as they differentiate from naïve T cells to effectors or regulatory subsets. Given the
central role of the transcription factor Bhlhe40 in regulating effector function and IL-10 production, we will also
test its role in parasite-specific T cell fates and the development of a Tr1 phenotype which may provide
immune tolerance to these parasites. In Aim 1 we will characterize the anti-parasite T cell response to H.
polygyrus. In Aim 2, we will evaluate the mechanisms that regulate immune tolerance to Cryptosporidium. In
Aim 3, we will determine how infection with these parasites impacts on the tolerogenic T cell response to food
antigens and on the induction of food allergy. Overall, these studies will provide novel and important insights
into how parasitic infections drive effector T cell responses to parasite antigens while simultaneously promoting
tolerogenic or pathogenic responses to food antigens.

## Key facts

- **NIH application ID:** 10841706
- **Project number:** 5R01AI162918-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Brian Todd Edelson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $631,050
- **Award type:** 5
- **Project period:** 2022-06-22 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841706

## Citation

> US National Institutes of Health, RePORTER application 10841706, Role of Intestinal Parasites on Regulating Immune Responses to Gut Antigens (5R01AI162918-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10841706. Licensed CC0.

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