Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages

Yifan Wang, Lamba Omar Sangare, Tatiana C. Paredes-Santos, Musa Hassan, Shruthi Krishnamurthy, Anna M. Furuta, Benedikt M. Markus, Sebastian Lourido, Jeroen P.J. Saeij

Research output: Contribution to journalArticlepeer-review

Abstract

Macrophages play an essential role in the early immune response against Toxoplasma and are the cell type preferentially infected by the parasite in vivo. Interferon gamma (IFNγ) elicits a variety of anti-Toxoplasma activities in macrophages. Using a genome-wide CRISPR screen we identified 353 Toxoplasma genes that determine parasite fitness in naїve or IFNγ-activated murine macrophages, seven of which we investigated and confirmed. We show that one of these genes encodes dense granule protein GRA45, which has a chaperone-like domain, is critical for correct localization of GRAs into the PVM and secretion of GRA effectors into the host cytoplasm. Parasites lacking GRA45 are more susceptible to IFNγ-mediated growth inhibition and have reduced virulence in mice. Together, we identified and characterized an important chaperone-like GRA in Toxoplasma and provided a resource for the community to further explore the function of Toxoplasma genes that determine fitness in IFNγ- activated macrophages.
Original languageEnglish
Article number5258 (2020)
JournalNature Communications
Volume11
Early online date16 Oct 2020
DOIs
Publication statusE-pub ahead of print - 16 Oct 2020

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