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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation*
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Antigens, CD*
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Antigens, Viral / genetics
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Antigens, Viral / immunology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / pathology
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Cell Line
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Dendritic Cells / immunology*
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Dendritic Cells / pathology
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Dogs
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / immunology
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Influenza A virus / genetics
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Influenza A virus / immunology*
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Integrin alpha Chains*
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Interferon Type I / genetics
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Interferon Type I / immunology
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Lung / immunology
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Lung / pathology
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Lung / virology
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Mice
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Orthomyxoviridae Infections / genetics
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / prevention & control*
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Receptor, Interferon alpha-beta / genetics
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Receptor, Interferon alpha-beta / immunology
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Signal Transduction / genetics
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Signal Transduction / immunology
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Viral Nonstructural Proteins / genetics
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Viral Nonstructural Proteins / immunology
Substances
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Antigens, CD
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Antigens, Viral
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INS1 protein, influenza virus
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Integrin alpha Chains
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Interferon Type I
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Recombinant Fusion Proteins
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Viral Nonstructural Proteins
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alpha E integrins
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Green Fluorescent Proteins
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Receptor, Interferon alpha-beta