# Impact of Toxoplasma gondii on Treg homeostasis

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2024 · $48,974

## Abstract

Project Summary/Abstract
Acute infection of mice with Toxoplasma gondii results in a collapse of the regulatory T cell (Treg)
population. While the infection-induced collapse of Treg cells has been defined, the re-building of
the compartment and the long-term impact of the crash have not been studied. Tregs were
originally believed to be a monolithic population of suppressor cells, but there is recognition of
distinct subsets termed central and effector Tregs. At homeostasis, central Tregs (cTregs) are a
relatively quiescent subset whereas effector Tregs (eTregs) exhibit hallmarks of recent TCR
engagement and potent suppressive activity. The studies presented here reveal that infection
results in a skewing of the composition of the Treg compartment after the collapse. My data shows
as infection resolves, there is restoration of IL-2 production and thymic output and the Treg
compartment returns to near normal levels, yet there remains a marked increase in the ratio of
cTreg:eTreg cells. The use of lineage tracing shows that the post-crash Treg compartment is
dominated by Treg cells that were present during collapse but a population of newly-generated
Tregs emerge from the thymus These observations raise fundamental questions about the
rebuilding process: (1) What cytokines contribute to re-population? (2) Does ongoing inflammation
associated with chronic infection affect Treg output and phenotype? And (3) Does the Treg
collapse lead to permanent alterations to the population structure or function of the Treg
compartment? To get at these questions, I will utilize high-parameter flow cytometry, multi-omic
sequencing and an in vivo Treg tracing model to investigate the Treg compartment throughout
infection with T.gondii. I will interrogate the impact of IL-2 and IL-7 on Treg re-population and
determine how infection shapes the re-built Treg compartment. These studies will enhance our
understanding of Treg biology during infection and identify possible approaches for manipulating
Treg subsets therapeutically.

## Key facts

- **NIH application ID:** 10901125
- **Project number:** 1F31AI179240-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Zachary R Lanzar
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901125

## Citation

> US National Institutes of Health, RePORTER application 10901125, Impact of Toxoplasma gondii on Treg homeostasis (1F31AI179240-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10901125. Licensed CC0.

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