# Parasite dissemination in Toxoplasmic encephalitis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $337,168

## Abstract

ABSTRACT/PROJECT SUMMARY
Toxoplasma gondii is an intracellular parasite that infects one-third of humans globally. T. gondii establishes
a chronic infection in the brain, and immune compromise due to HIV infection, organ transplantation, or
chemotherapy can lead to parasite reactivation and fatal encephalitis. This proposal addresses a poorly
understood aspect of parasite pathogenesis – how does T. gondii migrate through the brain? Evidence
suggests that T. gondii infection of migratory leukocytes, such as microglia and monocytes, facilitates their
dissemination. For the parent R01, the objective of the proposal is to define how T. gondii induces
monocyte motility and disseminates through the brain. Two aims were proposed to test the hypothesis:
1) Determine how T. gondii enhances the migration of infected cells, and 2) Define how T. gondii
disseminates through the infected brain. In the second aim, we have been using intravital two-photon
imaging of the brains of T. gondii-infected mice to define the myeloid cell type(s) that are infected and
potentiate parasite spread through the brain. Transgenic mice that express fluorescent monocytes or
microglia are infected with T. gondii, and the dynamics of their migration through the parenchyma is
determined during acute infection and in chronically-infected mice undergoing parasite reactivation.
Alzheimer’s disease is associated with an accumulation of amyloid b (Ab) plaques in the brain. Microglia are
found surrounding Ab plaques in Alzheimer’s disease mouse models, but these microglia are incapable of
clearing the amyloid. Interestingly, T. gondii infection of Alzheimer’s disease mouse models causes a
reduction in Ab plaques in the brain and improved cognition, but the mechanism of this neuroprotective
effect is poorly understood. Data we collected as part of the parent R01 show that T. gondii induces a
significant monocyte infiltration of the brain, which is associated with increased microglial activation. Based
on these data, we hypothesize that T. gondii infection of Alzheimer’s disease mice re-activates the
phagocytic potential of microglia and enhances their clearance of Ab plaques. The objective of the
Administrative Supplement is to utilize the same intravital imaging approaches we are using to
examine microglial dynamics in the parent R01 to determine how microglia respond to Ab plaques
during T. gondii infection of Alzheimer’s disease mice. The proposed experiments fit squarely within the
scope of Aim 2 of the parent R01, as the experimental workflow to track microglial responses in the brain is
currently being used to address Aim 2 of the parent R01. This proposal will leverage the resources of the
Alzheimer’s Disease Research Center (ADRC) at UC Irvine, a center of excellence funded by the NIA. The
significance of this research is that understanding how T. gondii infection alters amyloid dynamics may
allow for the development of therapeutic interventions to reduce neurotoxicity during Alzh...

## Key facts

- **NIH application ID:** 10123966
- **Project number:** 3R01AI120846-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Melissa Bruckner Lodoen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $337,168
- **Award type:** 3
- **Project period:** 2016-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123966

## Citation

> US National Institutes of Health, RePORTER application 10123966, Parasite dissemination in Toxoplasmic encephalitis (3R01AI120846-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123966. Licensed CC0.

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