Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Bioessays. 2011 Sep;33(9):693-700. doi: 10.1002/bies.201100054. Epub 2011 Jul 20.
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.
刚地弓形虫是一种非常成功的寄生虫，能够通过主动入侵有核宿主细胞并形成一个改良的隔间，在细胞质内复制，从而感染几乎所有温血动物。包含寄生虫的空泡为其提供了一个安全的避难所，即使是在巨噬细胞等专业吞噬细胞中也是如此，巨噬细胞通常会破坏外来微生物。为了消灭寄生虫，宿主上调了一组与免疫相关的 p47 GTPases（IRGs），这些 GTPases 被招募到包含寄生虫的空泡中，导致膜破裂和寄生虫消化。为了避免这种命运，高毒力的刚地弓形虫菌株在其空泡的外表面覆盖一层分泌丝氨酸/苏氨酸激酶，称为 ROP18。在这个宿主-病原体界面上，ROP18 磷酸化并使 IRGs 失活，从而保护寄生虫免受杀伤。这些发现揭示了寄生虫使宿主先天免疫失效的一种新的分子机制。
