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首页> 外文学位 >Respiratory syncytial virus subverts the immune response by inhibiting myeloid dendritic cell function.
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Respiratory syncytial virus subverts the immune response by inhibiting myeloid dendritic cell function.

机译：呼吸道合胞病毒通过抑制髓样树突状细胞功能破坏了免疫反应。

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摘要

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and young children. Antigen presentation by dendritic cells (DCs) is critical for the establishment of antiviral immunity and DCs are frequent targets of viral immune evasion. Upon activation, DCs undergo maturation during which they highly upregulate the surface expression of MHC class II, a molecule critical for the presentation of exogenous antigen to CD4+ T cells. MHC class II biosynthesis and surface expression is a multi-stage process which is controlled by a variety of positive and negative regulatory molecules. Here we show that DC exposed to RSV both in vivo and in vitro failed to elicit a mixed leukocyte reaction (MLR). Furthermore, RSV exposed DCs inhibited allogeneic proliferation from unexposed DCs in trans, in a cell contact dependent mechanism. Consistent with their impaired antigen presenting ability, both primary blood mDCs exposed in vitro to RSV and nasal mucosa mDC from RSV patients failed to upregulate MHC class II. MHC class II levels remained low despite the apparent upregulation of other markers of DC maturation such as MHC class I, CD83, CD86 and CD40. This inhibition could not be explained by the reduced bio-synthesis of MHC class II as class II transactivator (CIITA) level remained unchanged and the total cellular HLA-DR was comparable to mDCs exposed to influenza virus (FLU). Furthermore, SDS stability assay showed similar level of MHC class II peptide complex between the two viral treatments, indicating RSV exposure did not block class II loading. Consistent with the reduced surface expression, confocal microscopy demonstrated a selective blockade of MHC class II surface translocation by RSV. Blockade of class II surface translocation was dependent on viral fusion (F) protein expression. In addition, RSV induced the expression of a novel splice variant of HLA-DO, a negative regulatory molecule in the MHC class II presentation pathway. Taken together, these results demonstrate that RSV blocks DC antigen presentation by inhibiting surface class II peptide complex formation at multiple stages and suggest a novel mechanism of viral immune evasion.
机译：呼吸道合胞病毒（RSV）是婴幼儿下呼吸道感染的主要原因。树突状细胞（DC）的抗原呈递对于建立抗病毒免疫至关重要，而DC是病毒逃避免疫的常见靶标。激活后，DC会经历成熟，在此期间它们会高度上调MHC II类的表面表达，MHC II类是将外源抗原呈递给CD4 + T细胞的关键分子。 MHC II类生物合成和表面表达是一个多阶段过程，受多种正负调节分子控制。在这里，我们显示在体内和体外暴露于RSV的DC无法引发混合白细胞反应（MLR）。此外，在细胞接触依赖性机制中，暴露于RSV的DC反式抑制未暴露DC的同种异体增殖。与其抗原呈递能力受损相一致，体外暴露于RSV的原血mDC和来自RSV患者的鼻粘膜mDC均未上调II类MHC。尽管DC成熟的其他标志物（如MHC I类，CD83，CD86和CD40）明显上调，但MHC II类水平仍保持较低水平。由于II类反式激活因子（CIITA）的水平保持不变，并且细胞总HLA-DR与暴露于流感病毒（FLU）的mDC相当，因此不能通过II类MHC的生物合成减少来解释这种抑制作用。此外，SDS稳定性分析显示两种病毒处理之间的MHC II类肽复合物水平相似，表明RSV暴露并未阻断II类负荷。与减少的表面表达一致，共聚焦显微镜证实了RSV对MHC II类表面易位的选择性阻断。 II类表面易位的阻断取决于病毒融合（F）蛋白的表达。另外，RSV诱导了HLA-DO的新型剪接变体的表达，HLA-DO是MHC II类呈递途径中的负调控分子。综上所述，这些结果表明，RSV通过在多个阶段抑制表面II类肽复合物的形成来阻断DC抗原呈递，并提出了一种病毒逃避病毒的新机制。

著录项

  • 作者

    Xu, Chuang.;

  • 作者单位

    Baylor University.;

  • 授予单位 Baylor University.;
  • 学科 Biology Molecular.;Biology Cell.;Biology Virology.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 146 p.
  • 总页数 146
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;细胞生物学;
  • 关键词

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