AIREX: Host genetics highlights IFN-γ-dependent Toxoplasma genes encoding secreted and non-secreted virulence factors in in vivo CRISPR screens

タイトル	Host genetics highlights IFN-γ-dependent Toxoplasma genes encoding secreted and non-secreted virulence factors in in vivo CRISPR screens
DOI	https://doi.org/10.1016/j.celrep.2023.112592
本文（外部サイト）	https://ir.library.osaka-u.ac.jp/repo/ouka/all/92494/CellRep_42_6_112592.pdf
著者（英）	Tachibana, Yuta; Hashizaki, Emi; Sasai, Miwa; Yamamoto, Masahiro
発行日	2023-06-27
発行機関など	Elsevier B.V.
刊行物名	Cell Reports
巻	42
号	6
開始ページ	112592
言語	eng
内容記述	Tachibana Y., Hashizaki E., Sasai M., et al. Host genetics highlights IFN-γ-dependent Toxoplasma genes encoding secreted and non-secreted virulence factors in in vivo CRISPR screens. Cell Reports 42, 112592 (2023); https://doi.org/10.1016/j.celrep.2023.112592. Secreted virulence factors of Toxoplasma to survive in immune-competent hosts have been extensively explored by classical genetics and in vivo CRISPR screen methods, whereas their requirements in immune-deficient hosts are incompletely understood. Those of non-secreted virulence factors are further enigmatic. Here we develop an in vivo CRISPR screen system to enrich not only secreted but also non-secreted virulence factors in virulent Toxoplasma-infected C57BL/6 mice. Notably, combined usage of immune-deficient Ifngr1−/− mice highlights genes encoding various non-secreted proteins as well as well-known effectors such as ROP5, ROP18, GRA12, and GRA45 as interferon-γ (IFN-γ)-dependent virulence genes. The screen results suggest a role of GRA72 for normal GRA17/GRA23 localization and the IFN-γ-dependent role of UFMylation-related genes. Collectively, our study demonstrates that host genetics can complement in vivo CRISPR screens to highlight genes encoding IFN-γ-dependent secreted and non-secreted virulence factors in Toxoplasma.
キーワード	apicomplexa; CP: Immunology; CP: Microbiology; host genetics; host-pathogen interaction; IFN-γ; in vivo CRISPR screen; parasitophorous vacuole membrane; Toxoplasma; UFMylation; virulence genes
権利	This article is licensed under a Creative Commons Attribution 4.0 International License.
URI	https://repository.exst.jaxa.jp/dspace/handle/a-is/1235149