Synergistic role of micronemal proteins in Toxoplasma gondii virulence

被引:134
作者
Céréde, O
Dubremetz, JF
Soête, M
Deslée, D
Vial, H
Bout, D
Lebrun, M [1 ]
机构
[1] Univ Montpellier 2, UMR 5539, CNRS, F-34090 Montpellier, France
[2] UMR Univ, INRA Immunol Parasitaires, Fac Sci Pharmaceut & Biol, F-37200 Tours, France
[3] CNRS, FRE 2377, Inst Biol Lille, F-59021 Lille, France
基金
英国惠康基金;
关键词
D O I
10.1084/jem.20041672
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Apicomplexan parasites invade cells by a unique mechanism involving discharge of secretory vesicles called micronemes. Microneme proteins (MICs) include transmembrane and soluble proteins expressing different adhesive domains. Although the transmembrane protein TRAP and its homologues are thought to bridge cell surface receptors and the parasite submembranous motor, little is known about the function of other MICs. We have addressed the role of MIC1 and MIC3, two soluble adhesins of Toxoplasma gondii, in invasion and virulence. Single deletion of the MIC1 gene decreased invasion in fibroblasts, whereas MIC3 deletion had no effect either alone or in the mic1KO context. Individual disruption of MIC1 or MIC3 genes slightly reduced virulence in the mouse, whereas doubly depleted parasites were severely impaired in virulence and conferred protection against subsequent challenge. Single substitution of two critical amino acids in the chitin binding-like (CBL) domain of MIC3 abolished MIC3 binding to cells and generated the attenuated virulence phenotype. Our findings identify the CBL domain of MIC3 as a key player in toxoplasmosis and reveal the synergistic role of MICs in virulence, supporting the idea that parasites have evolved multiple ligand-receptor interactions to ensure invasion of different cells types during the course of infection.
引用
收藏
页码:453 / 463
页数:11
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