Cross-presenting CD103+ dendritic cells are protected from influenza virus infection
Cross-presenting CD103+ dendritic cells are protected from influenza virus infection
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DOI：
10.1172/jci60659
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发表时间：
2012-11-01
影响因子：
15.9
通讯作者：
Merad, Miriam
中科院分区：
文献类型：
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作者：
Helft, Julie;Manicassamy, Balaji;Merad, Miriam
当流感病毒感染时，CD8(+)细胞毒性T细胞对病毒从肺部清除至关重要。树突状细胞的抗原交叉提呈在诱导抗病毒细胞毒性T细胞中的作用仍然存在争议。在这里，我们使用了一种表达非结构1-GFP(NS1-GFP)报告基因的重组流感病毒来可视化小鼠肺树突状细胞在病毒感染时的抗原提呈途径。我们发现肺CD103(+)DC是唯一携带完整的GFP蛋白到引流的LNS的细胞亚群。值得注意的是，肺移行CD103(+)DC不能被流感病毒产生感染，因此能够通过病毒感染细胞的抗原交叉提呈来诱导病毒特异性CD8(+)T细胞。我们还观察到CD103(+)DC对感染的抵抗力与这些细胞中增强的抗病毒状态有关，这种状态依赖于I型干扰素受体的表达。这些结果表明，迁移的肺树突状细胞有效的交叉激发与获得抗病毒状态有关，这种状态依赖于I型干扰素信号通路。
CD8(+) cytotoxic T cells are critical for viral clearance from the lungs upon influenza virus infection. The contribution of antigen cross-presentation by DCs to the induction of anti-viral cytotoxic T cells remains controversial. Here, we used a recombinant influenza virus expressing a nonstructural 1-GFP (NS1-GFP) reporter gene to visualize the route of antigen presentation by lung DCs upon viral infection in mice. We found that lung CD103(+) DCs were the only subset of cells that carried intact GFP protein to the draining LNs. Strikingly, lung migratory CD103(+) DCs were not productively infected by influenza virus and thus were able to induce virus-specific CD8(+) T cells through the cross-presentation of antigens from virally infected cells. We also observed that CD103(+) DC resistance to infection correlates with an increased anti-viral state in these cells that is dependent on the expression of type I IFN receptor. These results show that efficient cross-priming by migratory lung DCs is coupled to the acquisition of an anti-viral status, which is dependent on the type I IFN signaling pathway.