title: Inhibition of ATF6β-dependent host adaptive immune response by a Toxoplasma virulence factor ROP18.
abstract: Toxoplasma gondii (T. gondii) secretes various effector molecules, which co-opt host cells and enable parasite proliferation. Of these, the rhoptry protein, ROP18, is a parasite-derived factor that determines acute virulence. ROP18 is injected into the host cytoplasm during infection and, eventually, localizes to parasitophorous vacuole (PV) membranes. ROP18 is predicted to be a serine/threonine kinase; however, the molecular mechanism by which ROP18 mediates its pathological effects remains unclear. At the end of 2010, two groups reported that ROP18 targets and phosphorylates interferon-inducible p47 small GTPases (IRGs), demonstrating the parasite's strategy for disarming the innate defense system. Recently, we described a mechanism by which ROP18 mediates degradation of the host endoplasmic reticulum-localizing transcription factor, ATF6β, to downregulate CD8 T cell-mediated type I adaptive immune responses. Taken together, these results suggest that T. gondii inactivates host innate and adaptive immune responses by targeting different host immunity-related molecules: IRGs and ATF6β.
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, and Laboratory of Mucosal Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000276:immunology*; D056704:Adaptive Immunity; D000818:Animals; D015536:Down-Regulation; D006790:Host-Parasite Interactions; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins; D014122:Toxoplasma / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology* / Q000469:parasitology; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D051702:Activating Transcription Factor 6; C574724:Atf6b protein, mouse; D015800:Protozoan Proteins; D037521:Virulence Factors; D017346:Protein Serine-Threonine Kinases; C556793:ROP18 protein, Toxoplasma gondii