TLR activation of Langerhans cell-like dendritic cells triggers an antiviral immune response
TLR activation of Langerhans cell-like dendritic cells triggers an antiviral immune response
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DOI：
10.4049/jimmunol.177.1.298
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发表时间：
2006-07-01
影响因子：
4.4
通讯作者：
Modlin, Robert L.
中科院分区：
文献类型：
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作者：
Renn, Claudia N.;Sanchez, David Jesse;Modlin, Robert L.
朗格汉斯细胞（LC）是树突状细胞（DC）的一个独特的子集，存在于表皮中，并作为抵御入侵皮肤的病原体的第一道防线。为了研究人LC在先天性免疫应答中的作用，我们检测了来源于CD 34（+）祖细胞的LC样DC的TLR表达和功能，并将其与来源于外周血单核细胞的DC（单核细胞来源的DC; Mo-DC）进行比较。LC样DCs和Mo-DCs表达的TLR 1 -10 mRNA水平相当。虽然许多TLR诱导的细胞因子模式在两种细胞类型之间是相似的，但与Mo-DC相比，用TLR 3激动剂poly（I：C）刺激在LC样DC中触发了显著更高量的IFN诱导的趋化因子CXCL 9（由IFN-γ诱导的单核因子）和CXCL 11（IFN-γ诱导的T细胞α化学引诱物）。TLR 3激活的LC样DC的上清液以I型IFN依赖的方式减少水泡性口炎病毒的细胞内复制。最后，CXCL 9与来自病毒感染的皮肤活检标本中的LC共定位。总之，我们的数据表明，LC表现出直接的抗病毒活性，这是依赖于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-gamma) and CXCL11 (IFN-gamma-inducible T cell alpha 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.