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

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 5

CD103+ DCs present an anti-viral state that protects them from viral infection.

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CD103+ DCs present an anti-viral state that protects them from viral inf...
(A) Heat map of mRNA transcript relative value comparing the microarray analysis of CD103+ DCs and alveolar macrophages (Mϕ) purified from the lung naive mice (n = 3). Red represents high relative expression, while blue represents low relative expression. (B and C) Quantitative PCR (qPCR) analysis of lung alveolar macrophages and CD103+ DCs purified from WT mice 12 hours after infection with 106 PFUs of NS1-GFP virus. mRNA levels are normalized for each population to the level of housekeeping gene 18S (n = 3). (D and E) Deep sequencing mRNA analysis of lung alveolar macrophages and CD103+ DCs purified from lungs of naive WT mice (steady state) (D) or mice infected 12 hours earlier with 106 PFUs of NS1-GFP virus. (E). Heat maps present the relative mRNA expression levels between CD103+ DCs and alveolar macrophages in the indicated mice. Red represents high relative expression, while blue represents low relative expression. (F and G) WT mice (F) and Ifnar1–/– mice (G) were injected intranasally with 106 PFUs of NS1-GFP or PBS. Twelve hours later, alveolar macrophages (F) and CD103+ DCs (F and G) were purified from the lungs of naive or infected mice and cultured in 96-well plates for 12 hours with 3 or 10 MOI of NS1-GFP virus in vitro. Graphs represent the percentage of GFP-positive cells measured by flow cytometry 12 hours after in vitro infection. The baseline GFP expression level is subtracted from the GFP expression after in vitro infection. Data are representative of 3 separate experiments.