# Impact of IL-27 on monocyte responses to Toxoplasma gondii infection

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2022 · $46,752

## Abstract

Project Summary
The cytokine IL-27 is a critical mechanism for restraining immune hyperactivity during infection. During
Toxoplasma gondii infection, the loss of IL-27 results in a lethal, CD4+ T cell mediated immune response as
well as elevated inflammatory cytokine responses and systemic thrombosis. How these mechanisms mediate
pathology, and possibly intersect with one another, is unclear. GM-CSF production by CD4+ T cells is
enhanced in IL-27 deficient mice, and we have recently observed that blockade of this cytokine leads to
survival of infected IL-27-/- mice. GM-CSF can enhance monocyte and macrophage responses as well as
contribute to immunothrombosis, suggesting that this may be a potential central mechanism by which IL-27
mediated protection is achieved. Additionally, we have observed that the loss of IL-27 results in enhanced
monopoiesis and monocyte responses to infection. Monocytes do not express the IL-27 receptor, but long-term
hematopoietic stem cells (LT-HSCs) do and can be skewed towards several differentiation pathways by IL-27.
Thus, we hypothesize that the loss of IL-27 leads to enhanced monocyte development during infection which
may in turn be impacted by GM-CSF during later stages of infection to mediate pathology. To test this, we will
analyze if HSC development and monocyte phenotypes are impacted by IL-27 during the early stages of
toxoplasmosis and if enhanced monocytes responses are pathological in this setting. This will be achieved
through a combination of cell transfers, high-dimensional flow cytometry, and scRNA-seq as well as selective
depletion experiments. We will then determine the mechanisms by which GM-CSF mediates pathology in the
absence of IL-27. This will be done by blocking GM-CSF during infection of IL-27-/- mice and analyzing the
immune parameters connected to pathology. Following this, the GM-CSF receptor will be selectively removed
from potential cell types to determine if this rescues IL-27 deficient mice during infection. Together, these
studies will enhance our understanding of cytokine driven pathologies and mechanisms of immune protection.

## Key facts

- **NIH application ID:** 10387151
- **Project number:** 1F31AI161962-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Daniel Aldridge
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387151

## Citation

> US National Institutes of Health, RePORTER application 10387151, Impact of IL-27 on monocyte responses to Toxoplasma gondii infection (1F31AI161962-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10387151. Licensed CC0.

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