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.
journal_name
Cell Host Microbejournal_title
Cell host & microbeauthors
Sangaré LO,Ólafsson EB,Wang Y,Yang N,Julien L,Camejo A,Pesavento P,Sidik SM,Lourido S,Barragan A,Saeij JPJdoi
10.1016/j.chom.2019.09.008subject
Has Abstractpub_date
2019-10-09 00:00:00pages
478-492.e8issue
4eissn
1931-3128issn
1934-6069pii
S1931-3128(19)30475-5journal_volume
26pub_type
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