Lee Heung Kyu, Lund Jennifer M, Ramanathan Balaji, Mizushima Noboru, Iwasaki Akiko
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Science. 2007 Mar 9;315(5817):1398-401. doi: 10.1126/science.1136880. Epub 2007 Feb 1.
Plasmacytoid dendritic cells (pDCs) detect viruses in the acidified endosomes by means of Toll-like receptors (TLRs). Yet, pDC responses to certain single-stranded RNA (ssRNA) viruses occur only after live viral infection. We present evidence here that the recognition of such viruses by TLR7 requires transport of cytosolic viral replication intermediates into the lysosome by the process of autophagy. In addition, autophagy was found to be required for the production of interferon-alpha by pDCs. These results support a key role for autophagy in mediating ssRNA virus detection and interferon-alpha secretion by pDCs and suggest that cytosolic replication intermediates of viruses serve as pathogen signatures recognized by TLR7.
浆细胞样树突状细胞(pDCs)通过Toll样受体(TLRs)在酸化的内体中检测病毒。然而,pDC对某些单链RNA(ssRNA)病毒的反应仅在活病毒感染后才会发生。我们在此提供证据表明,TLR7对这类病毒的识别需要通过自噬过程将胞质病毒复制中间体转运到溶酶体中。此外,发现自噬是pDC产生α干扰素所必需的。这些结果支持了自噬在介导pDC检测ssRNA病毒和分泌α干扰素中起关键作用,并表明病毒的胞质复制中间体作为被TLR7识别的病原体标志。