title: 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.affiliation: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Helft
authors.forename: Balaji
authors.initials: B
authors.lastname: Manicassamy
authors.forename: Pierre
authors.initials: P
authors.lastname: Guermonprez
authors.forename: Daigo
authors.initials: D
authors.lastname: Hashimoto
authors.forename: Aymeric
authors.initials: A
authors.lastname: Silvin
authors.forename: Judith
authors.initials: J
authors.lastname: Agudo
authors.forename: Brian D
authors.initials: BD
authors.lastname: Brown
authors.forename: Mirco
authors.initials: M
authors.lastname: Schmolke
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Miller
authors.forename: Marylene
authors.initials: M
authors.lastname: Leboeuf
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004285:Dogs; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D039001:Integrin alpha Chains; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; C085820:INS1 protein, influenza virus; D039001:Integrin alpha Chains; D007370:Interferon Type I; D011993:Recombinant Fusion Proteins; D017361:Viral Nonstructural Proteins; C091367:alpha E integrins; D049452:Green Fluorescent Proteins; D053633:Receptor, Interferon alpha-beta