# Neuronal Latency and Toxoplasma

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $758,145

## Abstract

Project Summary
Neurons are poorly recognized by the immune system which contributes to the ability of neurotropic
pathogens to persist in the CNS but there is evidence that T cells can promote clearance of these
organisms. For the parasite Toxoplasma gondii, T cell production of the cytokine IFN- is important for
resistance in the CNS because it activates hematopoietic and non-hematopoietic cells to control the
tachyzoite (lytic) stage of the infection. Conversely, in response to cellular stress T. gondii transforms to the
latent bradyzoite stage and forms long lived cysts in neurons. The lack of therapies that target the latent
stage of T. gondii is a significant impediment to the management of this infection. Current dogma holds that
because this stage is in neurons it evades immune surveillance and ensures chronicity. However, there is
accumulating evidence of a more active battle between the host and parasite in the CNS. These
observations indicate that T cell production of IFN- activates neurons to control T. gondii but the ability of
this parasite to persist may be because bradyzoites evade recognition and/or modulate cyst specific
responses. In support of this idea, comparisons between tachyzoite and bradyzoite specific responses
suggest that cyst-specific CD8+ T cells have reduced effector functions. To understand how T. gondii is
recognized in neurons and how the parasite can evade surveillance, novel transgenic reporter systems for
parasites will be combined with host reporters to track the fate of infected neurons in vivo. Additional
studies will determine the impact of IFN- on neurons and live imaging studies will visualize interactions
between T cells and infected neurons and if this results in parasite clearance or evasion of T cell activities.
The findings that emerge from these studies will have a significant impact on understanding how CD8+ T
cell-neuron interactions lead to pathogen control and will be relevant to other neurotropic infections and
neuroinflammatory conditions.

## Key facts

- **NIH application ID:** 10144865
- **Project number:** 1R01AI157247-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** CHRISTOPHER A HUNTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $758,145
- **Award type:** 1
- **Project period:** 2020-09-23 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144865

## Citation

> US National Institutes of Health, RePORTER application 10144865, Neuronal Latency and Toxoplasma (1R01AI157247-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10144865. Licensed CC0.

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