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

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. Roch, Melissa B. Lodoen, Maryse Lebrun () and Diana Marcela Penarete-Vargas ()
Additional contact information
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

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56128-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56128-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56128-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().