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Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages
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Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages
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Journal Article
Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages
2020
Overview
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 identify 353
Toxoplasma
genes that determine parasite fitness in naїve or IFNγ-activated murine macrophages, seven of which are further 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 identify and characterize an important chaperone-like GRA in
Toxoplasma
and provide a resource for the community to further explore the function of
Toxoplasma
genes that determine fitness in IFNγ-activated macrophages.
Using a genome-wide CRISPR screen, the authors here identify
Toxoplasma
genes that counteract the anti-parasitic activity of interferon gamma in murine macrophages. One of these genes, dense granule protein GRA45, is critical for the trafficking of GRA effectors and affects virulence in mice.
Publisher
Nature Publishing Group UK,Nature Portfolio
Subject
/ 13/109
/ 14/1
/ 42/47
/ 45/91
/ 64/60
/ 64/86
/ Animals
/ Female
/ Humanities and Social Sciences
/ Humans
/ Interferon-gamma - immunology
/ Male
/ Mice
/ Science
/ Toxoplasma - growth & development
