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The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death

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Listed:
  • Margarida T. Grilo Ruivo

    (Université de Montpellier)

  • Ji-hun Shin

    (University of California)

  • Todd Lenz

    (University of California Riverside)

  • Stephanie Y. Matsuno

    (University of California)

  • Katherine Olivia Yanes

    (University of California)

  • Arnault Graindorge

    (Université de Montpellier)

  • Maguy Hamie

    (American University of Beirut)

  • Laurence Berry-Sterkers

    (Université de Montpellier)

  • Mathieu Gissot

    (Center for Infection and Immunity of Lille)

  • Hiba El Hajj

    (American University of Beirut)

  • Karine G. Roch

    (University of California Riverside)

  • Melissa B. Lodoen

    (University of California)

  • Maryse Lebrun

    (Université de Montpellier)

  • Diana Marcela Penarete-Vargas

    (Université de Montpellier)

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.

Suggested Citation

  • 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, 2025. "The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56128-x
    DOI: 10.1038/s41467-025-56128-x
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    References listed on IDEAS

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    1. Corey Rogers & Teresa Fernandes-Alnemri & Lindsey Mayes & Diana Alnemri & Gino Cingolani & Emad S. Alnemri, 2017. "Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
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