SRP013843 PRJNA169091 GSE38838 Cross-presenting CD103+ dendritic cells are protected from influenza virus infection 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 GSE38838