Involvement of glycoreceptors in galactoxylomannan-induced T cell death.
Involvement of glycoreceptors in galactoxylomannan-induced T cell death.
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DOI：
10.4049/jimmunol.0803833
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发表时间：
2009-05-15
期刊：
影响因子：
--
通讯作者：
Vecchiarelli A
中科院分区：
文献类型：
--
作者：
Pericolini E;Gabrielli E;Cenci E;De Jesus M;Bistoni F;Casadevall A;Vecchiarelli A
新生隐球菌的主要毒力因子是其荚膜多糖，其也释放到组织中。脱落多糖由葡糖醛酸甘露聚糖（GXM）、半乳糖基甘露聚糖（GalXM）和甘露糖蛋白组成。在先前的研究中，我们证明了纯化的可溶性GalXM与诱导其凋亡的T细胞的直接相互作用。在这项研究中，我们专注于GalXM的凋亡作用的机制。在我们的实验系统中，我们分析了GalXM对纯化的人T细胞和Jurkat细胞（一种常规用于凋亡研究的T细胞系）的影响。我们的研究结果表明，GalXM激活的外部和内在的凋亡途径，通过切割和招募的caspase-8。Caspase-8通过Bid切割和caspase-9活化直接和间接地消除下游执行者caspase 3、6和7。这些作用似乎主要由GalXM与糖受体的相互作用介导，这在人T细胞和Jurkat细胞中不同。CD 45主要参与Jurkat细胞的凋亡，而CD 7和CD 43则介导人T细胞的凋亡。我们的研究结果强调了一种新的机制，通过这种机制，微生物产物可以通过与T细胞糖受体直接相互作用来促进毒力，从而引发淋巴细胞凋亡。
The major virulence factor of Cryptococcus neoformans is its capsular polysaccharide which is also released into tissues. The shed polysaccharide is composed of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoproteins. In a previous study, we demonstrated a direct interaction of purified soluble GalXM with T cells that induced their apoptosis. In this study, we focus on the mechanisms involved in the apoptotic effect of GalXM. In our experimental system, we analyzed the effect of GalXM on purified human T cells and Jurkat cells, a T cell line routinely used for apoptotic studies. Our results reveal that GalXM activates the extrinsic and intrinsic apoptotic pathways through the cleavage and recruitment of caspase-8. Caspase-8 elicits the downstream executioner caspases 3, 6, and 7 both directly and indirectly, via Bid cleavage and caspase-9 activation. These effects appeared to be primarily mediated by the interaction of GalXM with the glyco-receptors, which differed in human T and Jurkat cells. CD45 was primarily involved in Jurkat cells apoptosis while CD7 and CD43 mediated human T cell apoptosis. Our results highlight a new mechanism by which a microbial product can contribute to virulence through direct interaction with T cell glyco-receptors, thereby triggering lymphocyte apoptosis.
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影响因子：
3.7
作者：
Köhler B;Anguissola S;Concannon CG;Rehm M;Kögel D;Prehn JH
通讯作者：
Prehn JH
影响因子：
3.1
作者：
Chaka, W;Verheul, AFM;Hoepelman, IM
通讯作者：
Hoepelman, IM
DOI：
10.1006/bbrc.1999.0929
发表时间：
1999-07-05
影响因子：
3.1
作者：
Liu, J;Kuszynski, CA;Baxter, BT
通讯作者：
Baxter, BT
影响因子：
6.4
作者：
Monari, C;Pericolini, E;Vecchiarelli, A
通讯作者：
Vecchiarelli, A
影响因子：
7.2
作者：
Desharnais, Philippe;Dupere-Minier, Genevieve;Bernier, Jacques
通讯作者：
Bernier, Jacques