# T Regulatory cell responses in Toxoplasma-infected muscle

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $525,690

## Abstract

After a tissue is infected, the invading pathogen must be controlled and the tissue must be repaired or
else long-term morbidity and mortality will ensue. Toxoplasma gondii infections result in a
non-resolving chronic infection with tissue cysts residing preferentially in skeletal muscle and the
central nervous system. In contrast to the brain little is known about the immune response and
immune-regulation in the infected muscle. Foxp3-expressing CD4+ regulatory T cells (Tregs) play a
key role in controlling the immune response to infection and aid in tissue repair. Yet, we have found
during chronic T. gondii infection muscle Tregs become pathogenic and cause inflammation instead
of preventing it. We have shown these Tregs are Th1-polarized but do not produce IFNγ. Tregs in T.
gondii-infected muscle produce low levels of amphiregulin, a cytokine critical in repairing
immune-mediated pathology. We showed that Toxoplasma-induced immunopathology in muscle can
be ameliorated by recombinant treatment with amphiregulin in chronically infected mice and returning
function to the tissue. However it is unclear how amphiregulin mediates this effect. The overarching
hypothesis for this proposal is that T-bet expression in skeletal muscle Tregs drives this pathogenic
function by dampening production of key factors associated with normally suppressive Treg function.
This hypothesis will be addressed in the following specific aims: (1) identify how T-bet drives the
pathogenic function of Tregs in infected muscle and (2) define the role of amphiregulin in infected
muscle during Toxoplasma infection. How a chronic infection alters the highly orchestrated
immune-mediated regeneration of muscle is still poorly understood. Loss of muscle mass predicts
reduced quality of life and often increased morbidity for chronically ill patients and so a better
understanding of what drives this process is needed for directing therapeutic interventions.

## Key facts

- **NIH application ID:** 10761744
- **Project number:** 5R01AI162756-03
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** ELIZABETH WOHLFERT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $525,690
- **Award type:** 5
- **Project period:** 2022-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10761744

## Citation

> US National Institutes of Health, RePORTER application 10761744, T Regulatory cell responses in Toxoplasma-infected muscle (5R01AI162756-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10761744. Licensed CC0.

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