Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell Host Microbe. 2011 Jun 16;9(6):472-83. doi: 10.1016/j.chom.2011.04.015.
European and North American strains of the parasite Toxoplasma gondii belong to three distinct clonal lineages, type I, type II, and type III, which differ in virulence. Understanding the basis of Toxoplasma strain differences and how secreted effectors work to achieve chronic infection is a major goal of current research. Here we show that type I and III infected macrophages, a cell type required for host immunity to Toxoplasma, are alternatively activated, while type II infected macrophages are classically activated. The Toxoplasma rhoptry kinase ROP16, which activates STAT6, is responsible for alternative activation. The Toxoplasma dense granule protein GRA15, which activates NF-κB, promotes classical activation by type II parasites. These effectors antagonistically regulate many of the same genes, and mice infected with type II parasites expressing type I ROP16 are protected against Toxoplasma-induced ileitis. Thus, polymorphisms in determinants that modulate macrophage activation influence the ability of Toxoplasma to establish a chronic infection.
欧洲和北美的刚地弓形虫寄生虫菌株属于三个不同的克隆谱系，即 I 型、II 型和 III 型，它们在毒力上有所不同。了解弓形虫菌株差异的基础以及分泌效应物如何发挥作用以实现慢性感染是当前研究的主要目标。在这里，我们表明，I 型和 III 型感染的巨噬细胞（一种宿主对弓形虫免疫所必需的细胞类型）被交替激活，而 II 型感染的巨噬细胞被经典激活。刚地弓形虫的 rhoptry 激酶 ROP16 激活 STAT6，负责交替激活。刚地弓形虫致密颗粒蛋白 GRA15 激活 NF-κB，通过 II 型寄生虫促进经典激活。这些效应物拮抗地调节许多相同的基因，并且感染 II 型寄生虫表达 I 型 ROP16 的小鼠对弓形虫引起的回肠炎具有保护作用。因此，调节巨噬细胞激活的决定因素的多态性影响了弓形虫建立慢性感染的能力。
