Diebold Sandra S, Kaisho Tsuneyasu, Hemmi Hiroaki, Akira Shizuo, Reis e Sousa Caetano
Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
Science. 2004 Mar 5;303(5663):1529-31. doi: 10.1126/science.1093616. Epub 2004 Feb 19.
Interferons (IFNs) are critical for protection from viral infection, but the pathways linking virus recognition to IFN induction remain poorly understood. Plasmacytoid dendritic cells produce vast amounts of IFN-alpha in response to the wild-type influenza virus. Here, we show that this requires endosomal recognition of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce TLR7-dependent production of inflammatory cytokines. These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.
干扰素(IFNs)对于抵御病毒感染至关重要,但将病毒识别与干扰素诱导联系起来的途径仍知之甚少。浆细胞样树突状细胞对野生型流感病毒产生大量的α干扰素。在此,我们表明这需要对流感基因组RNA进行内体识别并通过Toll样受体7(TLR7)和髓样分化因子88(MyD88)进行信号传导。非病毒来源的单链RNA(ssRNA)分子也诱导TLR7依赖性炎性细胞因子的产生。这些结果确定ssRNA为TLR7的配体,并表明先天免疫系统的细胞感知内体ssRNA以检测RNA病毒感染。