Y-enterocolitica inhibits antigen degradation in dendritic cells

Y-enterocolitica inhibits antigen degradation in dendritic cells
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DOI:
10.1016/j.micinf.2008.04.014
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发表时间:
2008-06-01
影响因子:
5.8
通讯作者:
Autenrieth, Ingo B.
Autenrieth, Ingo B.
中科院分区:
医学3区
文献类型:
--
作者:
Adkins, Irena;Koeberle, Martin;Autenrieth, Ingo B.

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小肠结肠炎耶尔森菌(Ye)破坏树突状细胞(DC)致敏CD 4(+)T细胞的能力,表明Ye可能破坏可溶性抗原(Ag)的摄取和/或加工。为了研究此Ye-infected DC负载有荧光标记的卵清蛋白作为Ag摄取和加工的标记物,并通过流式细胞术、荧光测定法和显微镜分析。与未感染的细胞相比,野生型pYV(+)以及无质粒pYV(-)细菌将DC中的Ag降解抑制40%。pYV(-)感染的DC的显微镜分析显示,40%的DC含有细胞内细菌,而没有细胞内细菌的DC降解了更多的Ag。当pYV-的内化被细胞松弛素D阻断时,Ag降解不再被抑制,表明细菌和卵清蛋白之间的降解竞争。与此相反,细胞松弛素D预处理的DC感染pYV+抑制Ag降解的机制依赖于存在的毒力质粒pYV编码YopE,YopH,YopM,YopP,YopT和YopO。由于没有单一的Yop抑制Ag降解,多个Yop的相互作用可能解释了这种效应,可能是通过抑制Rho GTP酶,因为在与C的毒素B孵育的DC中观察到Ag降解显著减少。很难然而,不能排除其他pYV编码因子的贡献。(C)2008年,Elsevier Masson SAS。All rights reserved.
Yersinia enterocolitica (Ye) disrupts the ability of dendritic cells (DC) to prime CD4(+) T cells suggesting that Ye may subvert uptake and/or processing of soluble antigens (Ag). To investigate this Ye-infected DC were loaded with fluorescently labelled ovalbumins as markers for Ag uptake and processing, and analysed by flow cytometry, fluorometry and microscopy. Wild type pYV(+) as well as plasmidless pYV(-) bacteria inhibited Ag degradation in DC by 40% compared to non-infected cells. Microscopic analyses of pYV(-)-infected DC revealed that 40% of DC contained intracellular bacteria, and that DC without intracellular bacteria had degraded more Ag. When internalization of pYV- was blocked by cytochalasin D, Ag degradation was no longer inhibited indicating the competition between degradation of bacteria and ovalbumin. In contrast, cytochalasin D pre-treated DC infected with pYV+ inhibited Ag degradation by a mechanism dependent on the presence of virulence plasmid pYV encoding YopE, YopH, YopM, YopP, YopT and YopO. As no single Yop inhibited Ag degradation, interaction of multiple Yops might account for this effect, possibly by inhibiting Rho GTPases, because of a significant decrease of Ag degradation observed in DC incubated with toxin B of C. difficile. However, the contribution of other pYV-encoded factors cannot be excluded. (C) 2008 Elsevier Masson SAS. All rights reserved.