TLR pathways and IFN-regulatory factors: To each its own

被引:144
作者
Colonna, Marco [1 ]
机构
[1] Washington Univ, Sch Med, St Louis, MO 63110 USA
关键词
interferons; TLR; virology;
D O I
10.1002/eji.200637009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
TLR trigger the induction of type I IFN (IFN-alpha/beta), providing a crucial mechanism of anti-viral defense. Until recently, TLR were thought to induce type I IFN responses by activating two transcription factors which belong to the IFN-regulatory factor (IRF) family, IRF-3 and IRF-7. TLR-3 and TLR-4 induce IFN-beta by activating IRF-3; TLR-9 induces IFN-alpha and IFN-beta through IRF-7, at least when engaged by type A CpG oligonucleotides (CpG-A) in plasmacytoid DC (pDC). In this issue of the European Journal of Immunology, it is demonstrated that TLR-9 induces IFN-beta when engaged by type B CpG oligonucleotides (CpG-B) in myeloid DC and macrophages. Remarkably, this response is independent of IRF-3/7 and, in fact, requires another IRF family member, IRF-1. IRF-1 is recruited by TLR-9 through the adaptor MyD88. Deficiency of the TLR-9 -> IRF-1 -> IFN-beta pathway results in impaired anti-viral responses not only in vitro but also in vivo. These results demonstrate that TLR induce IFN-alpha or IFN-beta responses by activating distinct IRF, depending on the TLR ligand and the cell type. These distinct TLR-IRF pathways may allow the immune system to tailor its responses to viral pathogens.
引用
收藏
页码:306 / 309
页数:4
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