TLR Activation of Langerhans Cell-Like Dendritic Cells Triggers an Antiviral Immune Response1

TLR Activation of Langerhans Cell-Like Dendritic Cells Triggers an Antiviral Immune Response1
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朗格汉斯细胞样树突状细胞的 TLR 激活触发抗病毒免疫反应1

DOI:
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发表时间:
2006
影响因子:
4.4
通讯作者:
R. Modlin
R. Modlin
中科院分区:
医学2区
文献类型:
--
作者:
C. Renn;D. J. Sanchez;M. Ochoa;A. Legaspi;C. Oh;Philip T Liu;S. Krutzik;P. Sieling;G. Cheng;R. Modlin

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朗格汉斯细胞(LC)是树突状细胞(DC)的一个独特亚群,存在于表皮中,是抵御病原体入侵皮肤的第一道防线。为了研究人LC在先天性免疫反应中的作用,我们检测了CD34+祖细胞来源的LC样树突状细胞的TLR表达和功能,并与外周血单核细胞来源的DC(单核细胞来源的DC;Mo-DC)进行了比较。类LC DC和Mo-DC表达TLR1-10mRNAs的水平相当。与Mo-DC相比,TLR3激动剂Poly(I:C)刺激LC样树突状细胞产生更多的干扰素诱导的趋化因子CXCL9(干扰素-γ诱导的单核细胞因子)和CXCL11(干扰素-γ诱导的T细胞α趋化因子)。TLR3激活的LC样树突状细胞的上清液以I型干扰素依赖的方式减少水泡性口炎病毒的细胞内复制。最后,在病毒感染皮肤活检标本中,CXCL9与LCS共定位。总之,我们的数据表明LCS显示出直接的抗病毒活性,这种活性依赖于I型干扰素作为先天免疫系统的一部分。
Langerhans cells (LC) are a unique subset of dendritic cells (DC), present in the epidermis and serving as the first line of defense against pathogens invading the skin. To investigate the role of human LCs in innate immune responses, we examined TLR expression and function of LC-like DCs derived from CD34+ progenitor cells and compared them to DCs derived from peripheral blood monocytes (monocyte-derived DC; Mo-DC). LC-like DCs and Mo-DCs expressed TLR1–10 mRNAs at comparable levels. Although many of the TLR-induced cytokine patterns were similar between the two cell types, stimulation with the TLR3 agonist poly(I:C) triggered significantly higher amounts of the IFN-inducible chemokines CXCL9 (monokine induced by IFN-γ) and CXCL11 (IFN-γ-inducible T cell α chemoattractant) in LC-like DCs as compared with Mo-DCs. Supernatants from TLR3-activated LC-like DCs reduced intracellular replication of vesicular stomatitis virus in a type I IFN-dependent manner. Finally, CXCL9 colocalized with LCs in skin biopsy specimens from viral infections. Together, our data suggest that LCs exhibit a direct antiviral activity that is dependent on type I IFN as part of the innate immune system.
DOI: 10.1006/bbrc.1993.1403
发表时间: 1993-04-15
影响因子: 3.1
作者:
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DOI: 10.1126/science.285.5428.736
发表时间: 1999-07-30
期刊: SCIENCE
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