Cross-presenting CD103+ dendritic cells are protected from influenza virus infection
| Autor: | Kenneth M. Murphy, Mirco Schmolke, Brian D. Brown, Daigo Hashimoto, Miriam Merad, Aymeric Silvin, Marylene Leboeuf, Balaji Manicassamy, Judith Agudo, Adolfo García-Sastre, Pierre Guermonprez, Julie Helft, Jennifer Miller |
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| Rok vydání: | 2012 |
| Předmět: |
viruses
Interferon Type I/genetics/immunology Receptor Interferon alpha-beta Signal Transduction/genetics/immunology CD8-Positive T-Lymphocytes Viral Nonstructural Proteins medicine.disease_cause Viral Nonstructural Proteins/genetics/immunology Mice Influenza A virus Cytotoxic T cell Antigens Viral Lung Antigen Presentation Green Fluorescent Proteins/genetics/immunology hemic and immune systems General Medicine Dendritic Cells/immunology/pathology Orthomyxoviridae Infections/genetics/immunology/prevention & control CD8-Positive T-Lymphocytes/immunology/pathology Interferon Type I Antigens Viral/genetics/immunology Integrin alpha Chains Research Article Signal Transduction Recombinant Fusion Proteins/genetics/immunology Recombinant Fusion Proteins Green Fluorescent Proteins Antigen presentation chemical and pharmacologic phenomena Biology Virus Cell Line Dogs Orthomyxoviridae Infections Antigen Antigens CD Influenza A virus/genetics/immunology medicine Animals Reporter gene Receptor Interferon alpha-beta/genetics/immunology Dendritic Cells Lung/immunology/pathology/virology Virology Cell culture Immunology CD8 |
| Zdroj: | Journal of Clinical Investigation, Vol. 122, No 11 (2012) pp. 4037-4047 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci60659 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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