Toxoplasma gondii GRA60 is an effector protein that modulates host cell autonomous immunity and contributes to virulence

Article Article scientifique Article Toxoplasma gondii GRA60 is an effector protein that modulates host cell autonomous immunity and contributes to virulence eng 2020 author Nyonda Mary 848497 author Hammoudi Pierre-Mehdi 811456 author Ye Shu 931418 author Maire Jessica 785912 author Marq Jean-Baptiste 27225 author Yamamoto Masahiro author Soldati-Favre Dominique 0000-0003-4156-2109 135114 e13278 10.1111/cmi.13278 33040458 1462-5814 https://onlinelibrary.wiley.com/doi/10.1111/cmi.13278 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. Dewey 616 Swiss National Science Foundation Cyst wall formation: a persistent challenge in Toxoplasmosis CRSII3_160702 CH Programmes European Commission Molecular Basis of Toxoplasma gondii Encystation and Persistence 695596 ToxoPersist EU H2020 54 Département de microbiologie et médecine moléculaire 21B false 443 Biologie d'un parasite intracellulaire obligatoire 773 Cellular Microbiology ae26dd4b-5cc5-4ad0-867a-e2f550e7c3c0 Article (Accepted version) Public Nyonda-1.pdf 6818893 application/pdf Restricted 2021-10-11 5a8c1dd3-0f1c-4da0-aa90-011e4e2dac79 Supplemental data Public cmi13278-sup-0001-supinfo.zip 6617170 application/zip Restricted 2021-10-11 openAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

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Toxoplasma gondii GRA60 is an effector protein that modulates host cell autonomous immunity and contributes to virulence	Cellular Microbiology			2020	384	233

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