title: The secreted kinase ROP18 defends Toxoplasma's border.
abstract: Toxoplasma gondii is a highly successful parasite capable of infecting virtually all warm-blooded animals by actively invading nucleated host cells and forming a modified compartment where it replicates within the cytosol. The parasite-containing vacuole provides a safe haven, even in professional phagocytes such as macrophages, which normally destroy foreign microbes. In an effort to eliminate the parasite, the host up-regulates a family of immunity-related p47 GTPases (IRGs), which are recruited to the parasite-containing vacuole, resulting in membrane rupture and digestion of the parasite. To avoid this fate, highly virulent strains of Toxoplasma coat the external surface of their vacuole with a secretory serine/threonine kinase, known as ROP18. At this host-pathogen interface, ROP18 phosphorylates and inactivates IRGs, thereby protecting the parasite from killing. These findings reveal a novel molecular mechanism by which the parasite disarms host innate immunity.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Fentress
authors.forename: L David
authors.initials: LD
authors.lastname: Sibley
mesh_terms: D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000737:chemistry; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry; D014122:Toxoplasma / Q000201:enzymology / Q000472:pathogenicity* / Q000502:physiology; D014123:Toxoplasmosis / Q000276:immunology* / Q000469:parasitology; D014617:Vacuoles / Q000201:enzymology*
chemical_list: D008565:Membrane Proteins; D015800:Protozoan Proteins; C090555:ROP 2 protein, Toxoplasma gondii; D017346:Protein Serine-Threonine Kinases; C556793:ROP18 protein, Toxoplasma gondii; D020558:GTP Phosphohydrolases