Toxoplasma gondii triggers phosphorylation and nuclear translocation of dendritic cell STAT1 while simultaneously blocking IFNγ-induced STAT1 transcriptional activity.
Toxoplasma gondii triggers phosphorylation and nuclear translocation of dendritic cell STAT1 while simultaneously blocking IFNγ-induced STAT1 transcriptional activity.
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DOI：
10.1371/journal.pone.0060215
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Denkers EY
中科院分区：
文献类型：
--
作者：
Schneider AG;Abi Abdallah DS;Butcher BA;Denkers EY
弓形虫主动调节精氨酸诱导的JAK/STAT信号通路以促进宿主内的存活，包括阻断IFNγ介导的STAT 1依赖性促炎基因表达。我们试图进一步表征受感染的鼠树突状细胞（DC）中STAT 1信号传导的抑制，因为这种细胞类型先前未被检测，但已知其作为体内感染的早期靶标。出乎意料的是，我们发现T.弓形虫感染单独诱导持续的STAT 1磷酸化和核转位在DC中的寄生虫株独立的方式。STAT 1磷酸化的维持需要主动入侵，但细胞内寄生虫复制是不稳定的。寄生虫棒状体蛋白ROP 16，最近被证明介导STAT 3和STAT 6磷酸化，STAT 1磷酸化不需要。T.弓形虫诱导协同STAT 1磷酸化和异常STAT 1复合物与IFNγ共有序列寡核苷酸的结合。尽管有这些发现，寄生虫感染阻断了STAT 1与IFNγ诱导基因Irf-1和Lrg 47的天然启动子的结合，沿着随后的基因表达。这些结果加强了寄生虫介导的阻断树突状细胞中IFNγ反应的重要性，同时表明T。单独的弓形虫诱导STAT 1磷酸化。
The protozoan Toxoplasma gondii actively modulates cytokine-induced JAK/STAT signaling pathways to facilitate survival within the host, including blocking IFNγ-mediated STAT1-dependent proinflammatory gene expression. We sought to further characterize inhibition of STAT1 signaling in infected murine dendritic cells (DC) because this cell type has not previously been examined, yet is known to serve as an early target of in vivo infection. Unexpectedly, we discovered that T. gondii infection alone induced sustained STAT1 phosphorylation and nuclear translocation in DC in a parasite strain-independent manner. Maintenance of STAT1 phosphorylation required active invasion but intracellular parasite replication was dispensable. The parasite rhoptry protein ROP16, recently shown to mediate STAT3 and STAT6 phosphorylation, was not required for STAT1 phosphorylation. In combination with IFNγ, T. gondii induced synergistic STAT1 phosphorylation and binding of aberrant STAT1-containing complexes to IFNγ consensus sequence oligonucleotides. Despite these findings, parasite infection blocked STAT1 binding to the native promoters of the IFNγ-inducible genes Irf-1 and Lrg47, along with subsequent gene expression. These results reinforce the importance of parasite-mediated blockade of IFNγ responses in dendritic cells, while simultaneously showing that T. gondii alone induces STAT1 phosphorylation.
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影响因子：
3.7
作者：
Leng J;Denkers EY
通讯作者：
Denkers EY
影响因子：
4.4
作者：
Kim, Seon-Kyeong;Fouts, Ashley E.;Boothroyd, John C.
通讯作者：
Boothroyd, John C.
影响因子：
4
作者：
Dubey, J. P.;Velmurugan, G. V.;Su, C.
通讯作者：
Su, C.
DOI：
10.4049/jimmunol.182.1.489
发表时间：
2009-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Leng J;Butcher BA;Egan CE;Abi Abdallah DS;Denkers EY
通讯作者：
Denkers EY
影响因子：
30.3
作者：
Jensen KD;Wang Y;Wojno ED;Shastri AJ;Hu K;Cornel L;Boedec E;Ong YC;Chien YH;Hunter CA;Boothroyd JC;Saeij JP
通讯作者：
Saeij JP