Autophagy-dependent viral recognition by plasmacytoid dendritic cells

Autophagy-dependent viral recognition by plasmacytoid dendritic cells
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DOI:
10.1126/science.1136880
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发表时间:
2007-03-09
期刊:
影响因子:
56.9
通讯作者:
Iwasaki, Akiko
Iwasaki, Akiko
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lee, Heung Kyu;Lund, Jennifer M.;Iwasaki, Akiko

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浆细胞样树突状细胞(pDCs)通过toll样受体(TLRs)检测酸化核内体中的病毒。然而,pDC对某些单链RNA (ssRNA)病毒的应答仅在活病毒感染后发生。我们在此提供的证据表明,TLR7识别这类病毒需要通过自噬过程将细胞质病毒复制中间体转运到溶酶体中。此外,自噬被发现是pDCs产生干扰素- α所必需的。这些结果支持自噬在介导ssRNA病毒检测和pDCs分泌干扰素α中起关键作用,并表明病毒的细胞质复制中间体是TLR7识别的病原体特征。
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.