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

Tachibana, Yuta; Hashizaki, Emi; Sasai, Miwa et al.

Cell Reports, 2023, 42(6), 112592

Number of Access:461（2025-08-18 12:29 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/92494

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Title
Host genetics highlights IFN-γ-dependent Toxoplasma genes encoding secreted and non-secreted virulence factors in in vivo CRISPR screens
Creator
CreatorName
Tachibana, Yuta
CreatorName
Hashizaki, Emi
NRID
1000030631551 1000030631551
ORCID
0000-0001-6440-3958 0000-0001-6440-3958
researchmap permalink
miwa-s miwa-s
Scopus Author ID
16319941500 16319941500
CreatorName
Sasai, Miwa
NRID
1000000444521 1000000444521
researchmap permalink
read0151116 read0151116
Scopus Author ID
55552856200 55552856200
CreatorName
Yamamoto, Masahiro
Subject
apicomplexa
CP: Immunology
CP: Microbiology
host genetics
host-pathogen interaction
IFN-γ
in vivo CRISPR screen
parasitophorous vacuole membrane
Toxoplasma
UFMylation
virulence genes
Description
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.
Abstract
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.
Publisher
Elsevier B.V.
Source Title
Cell Reports
Volume (Issue)
42(6)
Page
112592
Date of Issued
2023-06-27
Language
English
Handle URL
https://hdl.handle.net/11094/92494
eISSN
22111247
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1016/j.celrep.2023.112592
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article