In Vivo CRISPR Screen Identifies TgWIP as a Toxoplasma Modulator of Dendritic Cell Migration.

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ID: 60323
2019
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Abstract
Toxoplasma can reach distant organs, especially the brain, leading to a lifelong chronic phase. However, genes involved in related in vivo processes are currently unknown. Here, we use focused CRISPR libraries to identify Toxoplasma genes that affect in vivo fitness. We focus on TgWIP, whose deletion affects Toxoplasma dissemination to distant organs. We show that TgWIP is secreted into the host cell upon invasion and interacts with the host WAVE regulatory complex and SHP2 phosphatase, both of which regulate actin dynamics. TgWIP affects the morphology of dendritic cells and mediates the dissolution of podosomes, which dendritic cells use to adhere to extracellular matrix. TgWIP enhances the motility and transmigration of parasitized dendritic cells, likely explaining its effect on in vivo fitness. Our results provide a framework for systemic identification of Toxoplasma genes with in vivo effects at the site of infection or on dissemination to distant organs, including the brain.
Reference Key
sangar2019invivocell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Sangaré, Lamba Omar;Ólafsson, Einar B;Wang, Yifan;Yang, Ninghan;Julien, Lindsay;Camejo, Ana;Pesavento, Patricia;Sidik, Saima M;Lourido, Sebastian;Barragan, Antonio;Saeij, Jeroen P J;
Journal cell host & microbe
Year 2019
DOI
S1931-3128(19)30475-5
URL
Keywords
Migration virulence dissemination toxoplasma gondii cyst crispr actin wave complex dendritic cell motility loss-of-function screen

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