Toxoplasma gondii GRA60 is an effector protein that modulates host cell autonomous immunity and contributes to virulence
| Autor: | Mary Nyonda, Jessica Maire, Dominique Soldati-Favre, Shu Ye, Masahiro Yamamoto, Pierre-Mehdi Hammoudi, Jean-Baptiste Marq |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Foreskin Immunology Protozoan Proteins Virulence Antigens Protozoan Vacuole Protein Serine-Threonine Kinases Microbiology GTP Phosphohydrolases Host-Parasite Interactions Gene Knockout Techniques Interferon-gamma Mice 03 medical and health sciences Immunity Virology parasitic diseases Animals Humans Pathogen IRGs 030304 developmental biology ddc:616 0303 health sciences biology 030306 microbiology Effector Toxoplasma gondii DNA Protozoan Fibroblasts biology.organism_classification Cell biology Mice Inbred C57BL Mutation Vacuoles Dense granule Toxoplasma Toxoplasmosis |
| Zdroj: | Cellular Microbiology (2020) P. e13278 |
| ISSN: | 1462-5822 1462-5814 |
| DOI: | 10.1111/cmi.13278 |
| Popis: | Toxoplasma gondii infects virtually any nucleated cell and resides inside a non‐phagocytic vacuole surrounded by a parasitophorous vacuolar membrane (PVM). Pivotal to the restriction of T. gondii dissemination upon infection in murine cells is the recruitment of Immunity Regulated GTPases (IRGs) and Guanylate Binding Proteins (GBPs) to the PVM that leads to pathogen elimination. The virulent T. gondii type I RH strain secretes a handful of effectors including the dense granule protein GRA7, the serine‐threonine kinases ROP17 and ROP18, and a pseudo‐kinase ROP5, that synergistically inhibit the recruitment of IRGs to the PVM. Here, we characterize GRA60, a novel dense granule effector which localizes to the vacuolar space and PVM and contributes to virulence of RH in mice suggesting a contribution to the subversion of host cell defense mechanisms. Members of the host cell IRG defense system Irgb10 and Irga6 are recruited to the PVM of RH parasites lacking GRA60 as observed previously for the avirulent RHΔrop5 mutant, with RH preventing such recruitment. Deletion of GRA60 in RHΔrop5 leads to a recruitment of IRGs comparable to the single knockouts. GRA60 therefore represents a novel parasite effector conferring resistance to IRGs in type I parasites, and is found to associate with ROP18, a member of the virulence complex. |
| Databáze: | OpenAIRE |
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