Migratory activation of parasitized dendritic cells by the protozoan Toxoplasma gondii 14-3-3 protein.
Migratory activation of parasitized dendritic cells by the protozoan Toxoplasma gondii 14-3-3 protein.
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DOI：
10.1111/cmi.12595
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发表时间：
2016-11
影响因子：
3.4
通讯作者：
Barragan A
中科院分区：
文献类型：
--
作者：
Weidner JM;Kanatani S;Uchtenhagen H;Varas-Godoy M;Schulte T;Engelberg K;Gubbels MJ;Sun HS;Harrison RE;Achour A;Barragan A
专性细胞内寄生虫弓形虫利用免疫系统的细胞进行传播。感染后，寄生的树突状细胞（DC）和小胶质细胞在体外表现出超迁移表型，这与增强小鼠体内寄生虫传播有关。一个尚未解决的问题是寄生虫如何通过“特洛伊木马”机制征用被寄生的细胞来实现系统传播。通过色谱和质谱分析，我们鉴定了14-3-3蛋白家族的一个直向同源物T。gondii 14-3-3（Tg 14 -3-3）作为DC高运动性的介质。我们证明，寄生虫衍生的多肽馏分富集Tg 14 -3-3或重组Tg 14 -3-3是足够的，以诱导高运动表型时，通过蛋白转染到鼠DC，人DC或小胶质细胞。此外，通过慢病毒转导的Tg 14 -3-3基因转移诱导原代人DC的运动性增强。在以配体可调节的方式表达Tg 14 -3-3的寄生虫中，Tg 14 -3-3的过表达与寄生的DC中的高运动性的诱导相关。在感染的DC中的定位研究鉴定了在寄生虫空泡空间内的Tg 14 -3-3和宿主细胞14-3-3向寄生虫空泡膜的快速募集。目前的工作确定了Tg 14 -3-3在T.刚地。总的来说，这些发现揭示了Tg 14 -3-3作为细胞内病原体的新靶标，其通过劫持宿主细胞的迁移特性来传播。
The obligate intracellular parasite Toxoplasma gondii exploits cells of the immune system to disseminate. Upon infection, parasitized dendritic cells (DCs) and microglia exhibit a hypermigratory phenotype in vitro that has been associated with enhancing parasite dissemination in vivo in mice. One unresolved question is how parasites commandeer parasitized cells to achieve systemic dissemination by a ‘Trojan horse’ mechanism. By chromatography and mass spectrometry analyses, we identified an orthologue of the 14-3-3 protein family, T. gondii 14-3-3 (Tg14-3-3), as mediator of DC hypermotility. We demonstrate that parasite-derived polypeptide fractions enriched for Tg14-3-3 or recombinant Tg14-3-3 are sufficient to induce the hypermotile phenotype when introduced by protein transfection into murine DCs, human DCs or microglia. Further, gene transfer of Tg14-3-3 by lentiviral transduction induced hypermotility in primary human DCs. In parasites expressing Tg14-3-3 in a ligand regulatable fashion, over-expression of Tg14-3-3 was correlated with induction of hypermotility in parasitized DCs. Localization studies in infected DCs identified Tg14-3-3 within the parasitophorous vacuolar space and a rapid recruitment of host cell 14-3-3 to the parasitophorous vacuole membrane. The present work identifies a determinant role for Tg14-3-3 in the induction of the migratory activation of immune cells by T. gondii. Collectively, the findings reveal Tg14-3-3 as a novel target for an intracellular pathogen that acts by hijacking the host cell’s migratory properties to disseminate.
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影响因子：
4.8
作者：
Lalle, Marco;Curra, Chiara;Ponzi, Marta
通讯作者：
Ponzi, Marta
影响因子：
3.1
作者：
Lambert, Henrik;Vutova, Polya P.;Barragan, Antonio
通讯作者：
Barragan, Antonio
影响因子：
3.3
作者：
BLASI, E;BARLUZZI, R;BISTONI, F
通讯作者：
BISTONI, F
影响因子：
3.1
作者：
Dellacasa-Lindberg, Isabel;Fuks, Jonas M.;Barragan, Antonio
通讯作者：
Barragan, Antonio
影响因子：
7.3
作者：
Freeman, Alyson K.;Morrison, Deborah K.
通讯作者：
Morrison, Deborah K.