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Cross-presenting CD103+ dendritic cells are protected from influenza virus infection
Julie Helft, … , Adolfo García-Sastre, Miriam Merad
Julie Helft, … , Adolfo García-Sastre, Miriam Merad
Published October 8, 2012
Citation Information: J Clin Invest. 2012;122(11):4037-4047. https://doi.org/10.1172/JCI60659.
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Research Article

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

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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.

Authors

Julie Helft, Balaji Manicassamy, Pierre Guermonprez, Daigo Hashimoto, Aymeric Silvin, Judith Agudo, Brian D. Brown, Mirco Schmolke, Jennifer C. Miller, Marylene Leboeuf, Kenneth M. Murphy, Adolfo García-Sastre, Miriam Merad

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Figure 1

Tracking viral antigens during influenza infection in vivo.

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Tracking viral antigens during influenza infection in vivo.
C57BL/6 mice...
C57BL/6 mice were infected intranasally with 106 PFUs of NS1-GFP virus. (A) Six hours post infection (p.i.), GFP levels were assessed by flow cytometry in CD45+ lung cells: MHCIIhiCD11c+CD103+ DC (gate 2), MHCIIhiCD11c+CD11b+ DC (gate 2), SSChiMHCIIloCD11c+CD103–macrophages (gate 1), and epithelial CD45– cells. Lower panels show a representative percentage of GFP+ cells gated among each lung population. Graph represents the percentage of GFP+ cells among live lung cells. (B) Images show GFP expression in lung sections 6 hours after infection stained with anti-langerin and anti-CD169 Abs and analyzed by confocal microscopy. White arrows show CD169+ macrophage and langerin+ DCs. Original magnification, ×40, zoom 6. (C) Percentage of total DCs (left panel) or GFP+ DCs (right panel) among live lung cells at the indicated time points after infection (n = 3). (D) Representative dot plots showing the percentage of each DC population in the lung 48 hours after infection (left panel) and the percentage of GFP+ cells in each lung DC subset (middle and right panels). (E) Dot plots show the percentage of GFP expression in each MLN DC subset 48 hours after infection. Gating strategy is described in Supplemental Figure 1F. (F) Absolute numbers of total DC subsets (lower panel) or GFP+ DC subsets (upper panel) in the MLNs at the indicated time points after NS1-GFP infection. (G) Images show GFP expression in MLN sections isolated 48 hours after infection, stained with anti-langerin and anti-CD169 mAbs, and analyzed by confocal microscopy. White arrows show CD169+ subcapsular macrophage and langerin+ DCs. Original magnification ×40, zoom 6.

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