The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death
Abstract Programmed-cell death is an antimicrobial defense mechanism that promotes clearance of intracellular pathogens. Toxoplasma counteracts host immune defenses by secreting effector proteins into host cells; however, how the parasite evades lytic cell death and the effectors involved remain poo...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56128-x |
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| author | Margarida T. Grilo Ruivo Ji-hun Shin Todd Lenz Stephanie Y. Matsuno Katherine Olivia Yanes Arnault Graindorge Maguy Hamie Laurence Berry-Sterkers Mathieu Gissot Hiba El Hajj Karine G. Le Roch Melissa B. Lodoen Maryse Lebrun Diana Marcela Penarete-Vargas |
| author_facet | Margarida T. Grilo Ruivo Ji-hun Shin Todd Lenz Stephanie Y. Matsuno Katherine Olivia Yanes Arnault Graindorge Maguy Hamie Laurence Berry-Sterkers Mathieu Gissot Hiba El Hajj Karine G. Le Roch Melissa B. Lodoen Maryse Lebrun Diana Marcela Penarete-Vargas |
| author_sort | Margarida T. Grilo Ruivo |
| collection | DOAJ |
| description | Abstract Programmed-cell death is an antimicrobial defense mechanism that promotes clearance of intracellular pathogens. Toxoplasma counteracts host immune defenses by secreting effector proteins into host cells; however, how the parasite evades lytic cell death and the effectors involved remain poorly characterized. We identified ROP55, a rhoptry protein that promotes parasite survival by preventing lytic cell death in absence of IFN-γ stimulation. RNA-Seq analysis revealed that ROP55 acts as a repressor of host pro-inflammatory responses. In THP-1 monocytes ΔROP55 infection increased NF-κB p65 nuclear translocation, IL-1β production, and GSDMD cleavage compared to wild type or complemented parasites. ΔROP55 infection also induced RIPK3-dependent necroptosis in human and mouse primary macrophages. Moreover, ΔROP55 parasites were significantly impaired in virulence in female mice and prevented NF-κB activation and parasite clearance in mBMDM. These findings place ROP55 as a major virulence factor, dampening lytic cell death and enabling Toxoplasma to evade clearance from infected cells. |
| format | Article |
| id | doaj-art-79b316fdc2ee478281ce1de901531f2a |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Nature Communications |
| spelling | doaj-art-79b316fdc2ee478281ce1de901531f2a2025-01-19T12:30:26ZengNature PortfolioNature Communications2041-17232025-01-0116111910.1038/s41467-025-56128-xThe Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell deathMargarida T. Grilo Ruivo0Ji-hun Shin1Todd Lenz2Stephanie Y. Matsuno3Katherine Olivia Yanes4Arnault Graindorge5Maguy Hamie6Laurence Berry-Sterkers7Mathieu Gissot8Hiba El Hajj9Karine G. Le Roch10Melissa B. Lodoen11Maryse Lebrun12Diana Marcela Penarete-Vargas13Laboratory of Pathogens and Host Immunity, UMR 5294 CNRS, UA15 INSERM, Université de MontpellierDepartment of Molecular Biology and Biochemistry and the Institute for Immunology, University of CaliforniaDepartment of Molecular, Cell and Systems Biology, University of California RiversideDepartment of Molecular Biology and Biochemistry and the Institute for Immunology, University of CaliforniaDepartment of Molecular Biology and Biochemistry and the Institute for Immunology, University of CaliforniaLaboratory of Pathogens and Host Immunity, UMR 5294 CNRS, UA15 INSERM, Université de MontpellierDepartment of Experimental Pathology, Immunology and Microbiology, American University of BeirutLaboratory of Pathogens and Host Immunity, UMR 5294 CNRS, UA15 INSERM, Université de MontpellierU1019 - UMR 9017, Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of LilleDepartment of Experimental Pathology, Immunology and Microbiology, American University of BeirutDepartment of Molecular, Cell and Systems Biology, University of California RiversideDepartment of Molecular Biology and Biochemistry and the Institute for Immunology, University of CaliforniaLaboratory of Pathogens and Host Immunity, UMR 5294 CNRS, UA15 INSERM, Université de MontpellierLaboratory of Pathogens and Host Immunity, UMR 5294 CNRS, UA15 INSERM, Université de MontpellierAbstract Programmed-cell death is an antimicrobial defense mechanism that promotes clearance of intracellular pathogens. Toxoplasma counteracts host immune defenses by secreting effector proteins into host cells; however, how the parasite evades lytic cell death and the effectors involved remain poorly characterized. We identified ROP55, a rhoptry protein that promotes parasite survival by preventing lytic cell death in absence of IFN-γ stimulation. RNA-Seq analysis revealed that ROP55 acts as a repressor of host pro-inflammatory responses. In THP-1 monocytes ΔROP55 infection increased NF-κB p65 nuclear translocation, IL-1β production, and GSDMD cleavage compared to wild type or complemented parasites. ΔROP55 infection also induced RIPK3-dependent necroptosis in human and mouse primary macrophages. Moreover, ΔROP55 parasites were significantly impaired in virulence in female mice and prevented NF-κB activation and parasite clearance in mBMDM. These findings place ROP55 as a major virulence factor, dampening lytic cell death and enabling Toxoplasma to evade clearance from infected cells.https://doi.org/10.1038/s41467-025-56128-x |
| spellingShingle | Margarida T. Grilo Ruivo Ji-hun Shin Todd Lenz Stephanie Y. Matsuno Katherine Olivia Yanes Arnault Graindorge Maguy Hamie Laurence Berry-Sterkers Mathieu Gissot Hiba El Hajj Karine G. Le Roch Melissa B. Lodoen Maryse Lebrun Diana Marcela Penarete-Vargas The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death Nature Communications |
| title | The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death |
| title_full | The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death |
| title_fullStr | The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death |
| title_full_unstemmed | The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death |
| title_short | The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death |
| title_sort | toxoplasma rhoptry protein rop55 is a major virulence factor that prevents lytic host cell death |
| url | https://doi.org/10.1038/s41467-025-56128-x |
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