Viral infection and Toll-like receptor agonists induce a differential expression of type I and λ interferons in human plasmacytoid and monocyte-derived dendritic cells
Viral infection and Toll-like receptor agonists induce a differential expression of type I and λ interferons in human plasmacytoid and monocyte-derived dendritic cells
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DOI：
10.1002/eji.200324610
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发表时间：
2004-03-01
影响因子：
5.4
通讯作者：
Uzé, G
中科院分区：
文献类型：
--
作者：
Coccia, EM;Severa, M;Uzé, G
在人类中，I型干扰素（IFN）家族由13种IFN-α亚型、IFN-β和IFN-ω组成;新发现的IFN-样家族由IFN-α 1、IFN-β 2和IFN-β 3组成。我们研究了病毒感染或Toll样受体（TLR）触发单核细胞来源的DC（MDDC）和浆细胞样DC（pDC）后I型和λ IFN基因的表达。我们发现，所有IFN-α、IFN-β、IFN-ω和IFN-λ亚型都在流感病毒感染的MDDC或pDC中表达。相反，差异I型IFN基因转录诱导MDDC和pDC刺激特异性TLR激动剂。CpG DNA刺激TLR-9诱导pDC中所有IFN-α、IFN-β、IFN-ω和IFN-λ亚型的表达，而LPS刺激TLR-4或poly I：C刺激TLR-3仅诱导MDDC中IFN-β和IFN-λ基因表达。同时检测MDDC和pDC中IFN调节因子（IRF）-5和IRF-7的表达。IRF-5在两个DC亚群中组成型表达，而IRF-7在pDC中组成型表达，但其表达沿着MDDC成熟而诱导。总之，我们的数据表明，IFN-λ与IFN-β的协调表达对于DC的成熟至关重要。
In humans, the type I interferon (IFN) family consists of 13 IFN-alpha subtypes, IFN-beta and IFN-omega; the newly discovered IFN-like family consists of IFN-lambda1, -lambda2 and -lambda3. We have investigated the expression of type I and lambda IFN genes following virus infections or Toll-like receptor (TLR) triggering in monocyte-derived DC (MDDC) and plasmacytoid DC (pDC). We found that all IFN-alpha, -beta, -omega and -lambda subtypes are expressed in influenza-virus-infected MDDC or pDC. Conversely, differential type I IFN gene transcription was induced in MDDC and pDC stimulated by specific TLR agonists. TLR-9 stimulation by CpG DNA induced the expression of all IFN-alpha, -beta, -omega and -lambda subtypes in pDC, whereas TLR-4 stimulation by LPS, or TLR-3 stimulation by poly I:C, induced only IFN-beta and IFN-lambda, gene expression in MDDC. The expression pattern of IFN regulatory factor (IRF)-5 and IRF-7 in MDDC and pDC was also determined. IRF-5 was constitutively expressed in the two DC subsets whereas IRF-7 was constitutive in pDC but its expression was induced along MDDC maturation. Overall, our data indicate that the coordinated expression of IFN-lambda with IFN-beta would be of crucial importance for the maturation of DC.