# Neuroinflammation during cerebral Toxoplasma gondii infection

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $177,689

## Abstract

PROJECT SUMMARY
Toxoplasma gondii is an intracellular parasite that infects one-third of humans worldwide and can cause fatal
disease during co-infection of HIV/AIDS patients. The parasites establish a long-term brain infection, and
reactivation of the infection causes Toxoplasmic encephalitis in immune-compromised HIV/AIDS patients. T.
gondii is among the most common opportunistic parasitic infections in AIDS patients and is the leading cause
of focal CNS infection complicating AIDS. Although T cells are essential for protective immunity against T.
gondii, recent evidence indicates that myeloid cells, including monocytes, also play a key role in host defense.
The trafficking of inflammatory monocytes from the blood to the CNS during chronic T. gondii infection is
critical for host protection against cerebral toxoplasmosis. Despite the important role of monocytes in CNS
immunity against T. gondii infection, remarkably little is known about the chemokines that drive monocyte
infiltration to the brain or the outcome of the neuroinflammatory response mediated by monocytes in the brain.
We recently performed a brain-wide imaging and neuroanatomical analysis of T. gondii infection in mice,
which revealed that inflammatory monocytes infiltrate the brain in a highly regionalized manner and
preferentially localize to the olfactory tubercle, a multisensory brain region involved in odor-guided behavior,
social and reward cognition, and behavioral flexibility. The objective of this proposal is to determine the
molecular cues that drive neuroinflammation during T. gondii infection and to define the outcome of this
response on the parasites and brain-resident cells. A model of chronic and reactivated T. gondii infection in
mice will be used. In this model, chronically-infected mice are subject to immune suppression to induce
parasite reactivation, thereby modeling the immune compromise of HIV/AIDS patients. In Aim 1, we will
localize inflammatory monocytes and T. gondii in the brains of mice during chronic and reactivated T. gondii
infection by performing light sheet microscopy on optically transparent, intact brains from infected transgenic
mice. We will also evaluate a role for astrocyte CCL2 in inflammatory monocyte infiltration of the CNS and in
parasite control by using mice deficient in astrocyte production of CCL2. In Aim 2, we will define the outcome
of the focal neuroinflammatory response on the parasites and on brain-resident cells during T. gondii infection.
We will investigate microglia and astrocyte activation, the levels of antimicrobial iNOS and IRG proteins, and
parasite burden in brain regions with high and low monocyte infiltration. We will also conduct an unbiased
RNA-Seq analysis comparing brain regions with high and low levels of infiltrating monocytes to determine the
effects of neuroinflammation on the transcriptional landscape during infection. This research is significant
because focal neuroinflammation may underlie a variety of CNS p...

## Key facts

- **NIH application ID:** 10374176
- **Project number:** 5R21AI155122-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Melissa Bruckner Lodoen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $177,689
- **Award type:** 5
- **Project period:** 2021-03-17 → 2025-03-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374176

## Citation

> US National Institutes of Health, RePORTER application 10374176, Neuroinflammation during cerebral Toxoplasma gondii infection (5R21AI155122-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10374176. Licensed CC0.

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