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J Clin Invest. 2012 Nov;122(11):4037-47. doi: 10.1172/JCI60659. Epub 2012 Oct 8.

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

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1
Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.

Abstract

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.

PMID:
23041628
PMCID:
PMC3484433
DOI:
10.1172/JCI60659
[Indexed for MEDLINE]
Free PMC Article

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