Toxoplasma gondii virulence factor ROP1 reduces parasite susceptibility to murine and human innate immune restriction.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
07
09
2022
accepted:
24
11
2022
revised:
19
12
2022
pubmed:
9
12
2022
medline:
22
12
2022
entrez:
8
12
2022
Statut:
epublish
Résumé
Toxoplasma gondii is an intracellular parasite that can infect many host species and is a cause of significant human morbidity worldwide. T. gondii secretes a diverse array of effector proteins into the host cell which are critical for infection. The vast majority of these secreted proteins have no predicted functional domains and remain uncharacterised. Here, we carried out a pooled CRISPR knockout screen in the T. gondii Prugniaud strain in vivo to identify secreted proteins that contribute to parasite immune evasion in the host. We demonstrate that ROP1, the first-identified rhoptry protein of T. gondii, is essential for virulence and has a previously unrecognised role in parasite resistance to interferon gamma-mediated innate immune restriction. This function is conserved in the highly virulent RH strain of T. gondii and contributes to parasite growth in both murine and human macrophages. While ROP1 affects the morphology of rhoptries, from where the protein is secreted, it does not affect rhoptry secretion. Finally, we show that ROP1 co-immunoprecipitates with the host cell protein C1QBP, an emerging regulator of innate immune signaling. In summary, we identify putative in vivo virulence factors in the T. gondii Prugniaud strain and show that ROP1 is an important and previously overlooked effector protein that counteracts both murine and human innate immunity.
Identifiants
pubmed: 36476844
doi: 10.1371/journal.ppat.1011021
pii: PPATHOGENS-D-22-01571
pmc: PMC9762571
doi:
Substances chimiques
C1QBP protein, human
0
Carrier Proteins
0
Mitochondrial Proteins
0
Protozoan Proteins
0
Virulence Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1011021Subventions
Organisme : Wellcome Trust
ID : FC001189
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001999
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001999
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001999
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_1202/10
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001189
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001189
Pays : United Kingdom
Informations de copyright
Copyright: © 2022 Butterworth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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