Virulence. 2012 Jan 1;3(1). [Epub ahead of print]
Inhibition of ATF6β-dependent host adaptive immune response by a Toxoplasma virulence factor ROP18.
Yamamoto M, Takeda K.
Department of Microbiology and Immunology; Graduate School of Medicine; and Laboratory of Mucosal Immunology; WPI Immunology Frontier Research Center; Osaka University; Suita, Osaka Japan.
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.
PMID: 22286708 [PubMed - as supplied by publisher]