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

Yuta Tachibana; Emi Hashizaki; Miwa Sasai; Masahiro Yamamoto

Cell Reports (Jun 2023)

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

Yuta Tachibana,
Emi Hashizaki,
Miwa Sasai,
Masahiro Yamamoto

Affiliations

Yuta Tachibana: Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan
Emi Hashizaki: Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan
Miwa Sasai: Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan; Department of Immunoparasitology, Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka 565-0871, Japan
Masahiro Yamamoto: Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan; Department of Immunoparasitology, Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka 565-0871, Japan; Corresponding author

Journal volume & issue: Vol. 42, no. 6
p. 112592

Abstract

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Summary: 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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