Uptake and intracellular trafficking of superantigens in dendritic cells.
Uptake and intracellular trafficking of superantigens in dendritic cells.
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DOI：
10.1371/journal.pone.0066244
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Malchiodi EL
中科院分区：
文献类型：
--
作者：
Ganem MB;De Marzi MC;Fernández-Lynch MJ;Jancic C;Vermeulen M;Geffner J;Mariuzza RA;Fernández MM;Malchiodi EL
细菌超抗原（SAg）是由金黄色葡萄球菌和化脓性链球菌产生的可引起中毒性休克综合征（TSS）的外毒素。根据目前的范例，SAg直接并同时与T细胞上的T细胞受体（TCR）和抗原呈递细胞（APC）上的MHC II类（MHC-II）相互作用，从而绕过细胞内加工以触发T细胞活化。树突状细胞（Dendritic cells，DC）是一种专职的APC，几乎覆盖所有的身体表面，并且是最有可能与SAg相互作用的候选者。我们证明了SAgs被小鼠DC吸收而不触发DC成熟。SAg作为生物活性分子存在于DC的细胞内酸性区室中。此外，SAgs共定位EEA 1，RAB-7和LAMP-2，在不同的时间，然后再循环到细胞膜。负载有SAg的DC能够触发体外淋巴细胞增殖，并且注射到小鼠中，刺激引流淋巴结中携带适当TCR的T细胞。SAg在DC中的运输和贩运可能增加这些外毒素的局部浓度，在那里它们将通过促进它们与淋巴结中的MHC-II和TCR两者的相遇而产生最高的效果，并且可以解释仅仅几个SAg分子如何能够诱导与TSS相关的严重病理。
Bacterial superantigens (SAgs) are exotoxins produced mainly by Staphylococcus aureus and Streptococcus pyogenes that can cause toxic shock syndrome (TSS). According to current paradigm, SAgs interact directly and simultaneously with T cell receptor (TCR) on the T cell and MHC class II (MHC-II) on the antigen-presenting cell (APC), thereby circumventing intracellular processing to trigger T cell activation. Dendritic cells (DCs) are professional APCs that coat nearly all body surfaces and are the most probable candidate to interact with SAgs. We demonstrate that SAgs are taken up by mouse DCs without triggering DC maturation. SAgs were found in intracellular acidic compartment of DCs as biologically active molecules. Moreover, SAgs co-localized with EEA1, RAB-7 and LAMP-2, at different times, and were then recycled to the cell membrane. DCs loaded with SAgs are capable of triggering in vitro lymphocyte proliferation and, injected into mice, stimulate T cells bearing the proper TCR in draining lymph nodes. Transportation and trafficking of SAgs in DCs might increase the local concentration of these exotoxins where they will produce the highest effect by promoting their encounter with both MHC-II and TCR in lymph nodes, and may explain how just a few SAg molecules can induce the severe pathology associated with TSS.
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影响因子：
64.8
作者：
Fields, BA;Malchiodi, EL;Mariuzza, RA
通讯作者：
Mariuzza, RA
影响因子：
56.9
作者：
Burgdorf, Sven;Kautz, Andreas;Kurts, Christian
通讯作者：
Kurts, Christian
影响因子：
2.9
作者：
Fernandez, Marisa M.;Bhattacharya, Suparna;Malchiodi, Emilio L.
通讯作者：
Malchiodi, Emilio L.
磷脂酰肌醇3-激酶和RAB5效应子在吞噬体生物发生和分枝杆菌吞噬体成熟停滞中的作用。
影响因子：
7.8
作者：
Fratti, R A;Backer, J M;Gruenberg, J;Corvera, S;Deretic, V
通讯作者：
Deretic, V
影响因子：
9.8
作者：
Arad G;Levy R;Nasie I;Hillman D;Rotfogel Z;Barash U;Supper E;Shpilka T;Minis A;Kaempfer R
通讯作者：
Kaempfer R