Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages.

Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages.
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液泡和质膜剥离以及自噬消除剂量巨噬细胞中的弓形虫弓形虫。

DOI:
10.1084/jem.20061318
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发表时间:
2006-09-04
影响因子:
15.3
通讯作者:
Yap, George S
Yap, George S
中科院分区:
医学1区
文献类型:
--
作者:
Ling, Yun M;Shaw, Michael H;Ayala, Carol;Coppens, Isabelle;Taylor, Gregory A;Ferguson, David J P;Yap, George S

文献摘要

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顶复合体原生动物病原体通过形成非融合性寄生物液泡(PV)来避免破坏并在宿主细胞内建立复制生态位。在这里,我们提出的证据,溶酶体介导的刚地弓形虫在体内活化的巨噬细胞入侵后降解。病原体的消除依赖于干扰素γ诱导的p47 GTPase, IGTP,需要PI3K活性,并且在PV膜压痕,囊泡,破坏之前,令人惊讶的是,寄生虫的质膜剥离。剥落的寄生虫被包裹在自噬体样液泡中,最终与溶酶体融合。这些观察结果概述了效应细胞使用的一系列机制,以将经典的非融合性细胞内病原体的命运转向免疫消除的途径。
Apicomplexan protozoan pathogens avoid destruction and establish a replicative niche within host cells by forming a nonfusogenic parasitophorous vacuole (PV). Here we present evidence for lysosome-mediated degradation of Toxoplasma gondii after invasion of macrophages activated in vivo. Pathogen elimination was dependent on the interferon γ inducible-p47 GTPase, IGTP, required PI3K activity, and was preceded by PV membrane indentation, vesiculation, disruption, and, surprisingly, stripping of the parasite plasma membrane. Denuded parasites were enveloped in autophagosome-like vacuoles, which ultimately fused with lysosomes. These observations outline a series of mechanisms used by effector cells to redirect the fate of a classically nonfusogenic intracellular pathogen toward a path of immune elimination.