Cross-presenting CD103+ dendritic cells are protected from influenza virus infection. Mus musculus

CD8+ cytotoxic T cells are critical for viral clearance from the lungs upon influenza virus infection. The contribution of cross-presentation to the induction of anti-viral cytotoxic T cells remains debated. Here, we used a recombinant influenza virus expressing a NS1-GFP reporter gene to visualize the route of antigen presentation by lung dendritic cells (DC) upon viral infection in vivo. We found that lung CD103+ DC are the only subset to carry intact GFP protein to the draining lymph nodes. Strikingly, lung migratory CD103+ DC are not productively infected by influenza virus and thus induce virus-specific CD8+ T cells through the cross-presentation of antigens from virally infected cells. We also show that CD103+ DC resistance to infection correlates with an increased antiviral state in these cells that is dependent on the expression of IFN receptor alpha. In conclusion, these results establish that efficient cross-priming by migratory lung DC is coupled to the acquisition of an anti-viral status, which is dependent on type I IFN signaling pathway. Overall design: mRNA profiles were generated by deep-sequencing in Illumina HiSeq2000 from alveolar macrophages and CD103+ dendritic cells from lungs of untreated and flu-treated mice

CD8+细胞毒性T细胞（CD8+ cytotoxic T cells）在流感病毒感染后，对肺部病毒清除至关重要。交叉呈递（cross-presentation）对抗病毒细胞毒性T细胞诱导的作用仍存在争议。本研究采用携带NS1-GFP报告基因的重组流感病毒，在体内可视化展示病毒感染后肺部树突状细胞（dendritic cells，DC）的抗原呈递途径。研究发现，肺部CD103+ DC是唯一能将完整GFP蛋白转运至引流淋巴结的细胞亚群。值得注意的是，肺部迁移性CD103+ DC并不会被流感病毒产毒性感染，因此它们通过交叉呈递病毒感染细胞的抗原，诱导病毒特异性CD8+细胞毒性T细胞。本研究同时证实，CD103+ DC的抗感染抗性与这类细胞的抗病毒状态增强相关，而该过程依赖于干扰素α受体（IFN receptor alpha）的表达。综上，本研究结果证实，肺部迁移性DC的高效交叉致敏（cross-priming）依赖于细胞获得的抗病毒状态，而该过程依赖于Ⅰ型干扰素信号通路。
实验设计：本研究通过Illumina HiSeq2000平台的深度测序，获取了未处理及流感病毒处理小鼠的肺泡巨噬细胞与肺部CD103+树突状细胞的mRNA表达谱。