Perry Andrea K, Chen Gang, Zheng Dahai, Tang Hong, Cheng Genhong
Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA.
Cell Res. 2005 Jun;15(6):407-22. doi: 10.1038/sj.cr.7290309.
Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNs are produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN production were largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type I IFN during viral infections by recognizing various viral components. Furthermore, much progress has been made in defining the signaling pathways downstream of TLRs for type I IFN production. TLR7 and TLR9 have become apparent as universally important in inducing type I IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellular viral pattern recognition receptors leading to type I IFN production have been identified. Many bacteria can also induce the up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type I IFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. This review will discuss the recent advances made in defining the signaling pathways leading to type I IFN production.
I型干扰素(IFN)是经过充分研究的具有抗病毒和免疫调节功能的细胞因子。I型干扰素在病毒感染后产生,但直到最近,导致干扰素产生的病毒识别机制在很大程度上仍不为人知。Toll样受体(TLR)通过识别各种病毒成分,已成为病毒感染期间I型干扰素的关键转导分子。此外,在确定TLR下游用于产生I型干扰素的信号通路方面已经取得了很大进展。TLR7和TLR9在大多数病毒感染期间,特别是浆细胞样树突状细胞诱导I型干扰素方面已明显成为普遍重要的分子。已鉴定出导致I型干扰素产生的新的细胞内病毒模式识别受体。许多细菌也可诱导这些细胞因子的上调。有趣的是,最近的研究发现,如果在细胞内革兰氏阳性细菌病原体单核细胞增生李斯特菌感染期间产生I型干扰素,对宿主细胞会产生有害影响。本综述将讨论在确定导致I型干扰素产生的信号通路方面取得的最新进展。