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Heterologous expression of interferon-stimulated genes reveals conserved anti-Toxoplasma properties between human and porcine cells

ABSTRACT: Toxoplasma is a zoonotic parasite that can cause life-threatening illness in humans and animals. The similarities in Toxoplasma pathogenesis between pigs and humans make pigs an attractive model for studying human toxoplasmosis. However, the mechanisms underpinning these similarities remain poorly understood. Since interferon-gamma (IFNg) is crucial for immunity to Toxoplasma, we hypothesized that IFNg signaling pathways conserved between humans and pigs contribute to comparable Toxoplasma pathogenesis. Using a genetic gain-of-function strategy, we observed that human or porcine interferon regulatory factor 1 (IRF1) and indoleamine 2,3-dioxygenase 1 (IDO1) inhibited Toxoplasma replication in both homologous and heterologous human and porcine cells. IRF1-depleted porcine cells that failed to control Toxoplasma growth could be rescued by ectopic expression of human IRF1, which induces genes similar to those regulated by porcine IRF1. Additionally, the expression of either human or pig IRF1 dampened Toxoplasma-induced transcriptional remodeling of porcine genes. These findings highlight conserved IFN-induced anti-Toxoplasma mechanisms between pigs and humans and enhance the potential of pigs as large animal models for human toxoplasmosis.

ORGANISM(S): Sus scrofa

PROVIDER: GSE326196 | GEO | 2026/03/28

REPOSITORIES: GEO

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