title: IFN-α enhances cross-presentation in human dendritic cells by modulating antigen survival, endocytic routing, and processing.
abstract: Cross-presentation allows antigen-presenting cells to present exogenous antigens to CD8(+) T cells, playing an essential role in controlling infections and tumor development. IFN-α induces the rapid differentiation of human mono-cytes into dendritic cells, known as IFN-DCs, highly efficient in mediating cross-presentation, as well as the cross-priming of CD8(+) T cells. Here, we have investigated the mechanisms underlying the cross-presentation ability of IFN-DCs by studying the intracellular sorting of soluble ovalbumin and nonstructural-3 protein of hepatitis C virus. Our results demonstrate that, independently from the route and mechanism of antigen entry, IFN-DCs are extraordinarily competent in preserving internalized proteins from early degradation and in routing antigens toward the MHC class-I processing pathway, allowing long-lasting, cross-priming capacity. In IFN-DCs, both early and recycling endosomes function as key compartments for the storage of both antigens and MHC-class I molecules and for proteasome- and transporter-associated with Ag processing-dependent auxiliary cross-presentation pathways. Because IFN-DCs closely resemble human DCs naturally occurring in vivo in response to infections and other danger signals, these findings may have important implications for the design of vaccination strategies in neoplastic or chronic infectious diseases.
authors.affiliation: Department of Cell Biology and Neurosciences, Section of Experimental Immunotherapy, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy;
authors.forename: Francesca
authors.initials: F
authors.lastname: Spadaro
authors.forename: Caterina
authors.initials: C
authors.lastname: Lapenta
authors.forename: Simona
authors.initials: S
authors.lastname: Donati
authors.forename: Laura
authors.initials: L
authors.lastname: Abalsamo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barnaba
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
authors.forename: Stefano M
authors.initials: SM
authors.lastname: Santini
authors.forename: Maria
authors.initials: M
authors.lastname: Ferrantini
mesh_terms: D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D045142:Cross-Priming / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects*; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D005434:Flow Cytometry; D016174:Hepacivirus / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016898:Interferon-alpha / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism / Q000493:pharmacokinetics; D017361:Viral Nonstructural Proteins / Q000276:immunology / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000941:Antigens; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D017361:Viral Nonstructural Proteins; C089383:nsp3 protein, alphavirus; D010047:Ovalbumin