# Toxoplasma effector-mediated modulation of innate immune pathways in non-murine macrophages

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $104,758

## Abstract

PROJECT SUMMARY
Toxoplasma gondii is an obligate intracellular parasite that causes severe disease in immunocompromised
individuals (e.g., AIDS patients) and fetuses. Its abilities to proliferate inside all nucleated cells and establish an
infection in almost all warm-blooded animals make the parasite an ideal model to study the mechanisms
involving in host-pathogen interaction. The outcome of Toxoplasma infection varies between host species. For
example, mice generally succumb to acute Toxoplasma infection while most non-murine hosts, such as rats
and humans, usually do not display symptoms but the chronic infection is established. As one of the cell types
determining the infection outcome, macrophages play an essential role in the early innate immune response
against Toxoplasma and coordinate the adaptive immune response. To successfully establish infection,
Toxoplasma co-opts host macrophages via parasite effectors secreted from its unique secretory organelles
(e.g., rhoptry and dense granule), named ROPs and GRAs, respectively. The role of Toxoplasma effectors has
been predominantly studied in murine macrophages, however, the effectors contributing to the infection in rat
and human macrophages are mostly unknown. My previous studies, together with preliminary data of this
project, identified several Toxoplasma effectors that specifically modulate the innate immune response in rat
but not murine macrophages. My central hypothesis is that Toxoplasma secretes a different set of parasite
effectors involved in the modulation of various innate immune responses to establish an infection in
macrophages from non-murine hosts. The goals during the K99 mentored phase are: 1) to understand the
mechanism of Toxoplasma effector-mediated activation of the NLRP1 inflammasome in rat macrophages; 2) to
mechanistically determine the role of Toxoplasma effectors that are required for parasite proliferation in naïve
rat macrophages. In the independent R00 phase, I will apply the training from the mentored phase to study the
interaction between Toxoplasma effectors and the innate immune response in human macrophages.
Specifically, I will identify fitness-conferring Toxoplasma secreted effectors and mainly determine parasite
effector-regulated host transcriptional responses in human macrophages. To accomplish these goals, valuable
training from a highly complementary mentor team with scientific and mentoring skills will guide my path to an
independent researcher. Furthermore, I will develop my leadership skills and strengthen my technical skills
through the proposed training. Collectively, the completion of this project will enhance our understanding of the
molecular mechanisms controlling host susceptibility to Toxoplasma infection. Also, knowing the parasite
effectors important for host modulation will provide better drug targets against toxoplasmosis.

## Key facts

- **NIH application ID:** 10460253
- **Project number:** 5K99AI163285-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Yifan Wang
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $104,758
- **Award type:** 5
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460253

## Citation

> US National Institutes of Health, RePORTER application 10460253, Toxoplasma effector-mediated modulation of innate immune pathways in non-murine macrophages (5K99AI163285-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10460253. Licensed CC0.

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