Thomas Jaime M, Pos Zoltan, Reinboth Jennifer, Wang Richard Y, Wang Ena, Frank Gregory M, Lusso Paolo, Trinchieri Giorgio, Alter Harvey J, Marincola Francesco M, Thomas Emmanuel
Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, CC, and Trans-NIH Center for Human Immunology (CHI), NIH, Bethesda, Maryland, USA.
MTA-Semmelweis University "Lendület" Experimental and Translational Immunomics Research Group, Budapest, HungaryInfectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, CC, and Trans-NIH Center for Human Immunology (CHI), NIH, Bethesda, Maryland, USA.
J Virol. 2014 Sep;88(18):10758-66. doi: 10.1128/JVI.01501-14. Epub 2014 Jul 9.
Plasmacytoid dendritic cells (pDCs) are key components of the innate immune response that are capable of synthesizing and rapidly releasing vast amounts of type I interferons (IFNs), particularly IFN-α. Here we investigated whether pDCs, often regarded as a mere source of IFN, discriminate between various functionally discrete stimuli and to what extent this reflects differences in pDC responses other than IFN-α release. To examine the ability of pDCs to differentially respond to various doses of intact and infectious HIV, hepatitis C virus, and H1N1 influenza virus, whole-genome gene expression analysis, enzyme-linked immunosorbent assays, and flow cytometry were used to investigate pDC responses at the transcriptional, protein, and cellular levels. Our data demonstrate that pDCs respond differentially to various viral stimuli with significant changes in gene expression, including those involved in pDC activation, migration, viral endocytosis, survival, or apoptosis. In some cases, the expression of these genes was induced even at levels comparable to that of IFN-α. Interestingly, we also found that depending on the viral entity and the viral titer used for stimulation, induction of IFN-α gene expression and the actual release of IFN-α are not necessarily temporally coordinated. In addition, our data suggest that high-titer influenza A (H1N1) virus infection can stimulate rapid pDC apoptosis.
Plasmacytoid dendritic cells (pDCs) are key players in the viral immune response. With the host response to viral infection being dependent on specific virus characteristics, a thorough examination and comparison of pDC responses to various viruses at various titers is beneficial for the field of virology. Our study illustrates that pDC infection with influenza virus, HIV, or hepatitis C virus results in a unique and differential response to each virus. These results have implications for future virology research, vaccine development, and virology as a whole.
浆细胞样树突状细胞（pDC）是先天性免疫反应的关键组成部分，能够合成并快速释放大量I型干扰素（IFN），尤其是IFN-α。在此，我们研究了通常被视为仅IFN来源的pDC是否能区分各种功能不同的刺激，以及这在多大程度上反映了除IFN-α释放之外pDC反应的差异。为了检测pDC对不同剂量完整和感染性HIV、丙型肝炎病毒及H1N1流感病毒的差异反应能力，我们使用全基因组基因表达分析、酶联免疫吸附测定及流式细胞术在转录、蛋白质和细胞水平研究pDC反应。我们的数据表明，pDC对各种病毒刺激有不同反应，基因表达有显著变化，包括参与pDC激活、迁移、病毒内吞、存活或凋亡的基因。在某些情况下，这些基因的表达甚至在与IFN-α相当的水平被诱导。有趣的是，我们还发现，根据病毒种类和用于刺激的病毒滴度，IFN-α基因表达的诱导和IFN-α的实际释放不一定在时间上协调一致。此外，我们的数据表明，高滴度甲型流感（H1N1）病毒感染可刺激pDC快速凋亡。
浆细胞样树突状细胞（pDC）是病毒免疫反应的关键参与者。由于宿主对病毒感染的反应取决于特定病毒特征，全面检查和比较pDC对不同滴度各种病毒的反应对病毒学领域有益。我们的研究表明，pDC感染流感病毒、HIV或丙型肝炎病毒会导致对每种病毒产生独特的差异反应。这些结果对未来病毒学研究及疫苗开发乃至整个病毒学都有影响。
