title: CD141+ dendritic cells produce prominent amounts of IFN-α after dsRNA recognition and can be targeted via DEC-205 in humanized mice.
abstract: Functional differences between human dendritic cell (DC) subsets and the potential benefits of targeting them with vaccines remain poorly defined. Here we describe that mice with reconstituted human immune system components (huNSG mice) develop all human conventional and plasmacytoid DC compartments in lymphoid organs. Testing different Toll-like receptor agonists for DC maturation in vivo, we found that IL-12p70 and interferon (IFN)-α production correlated with the maturation of CD141+ (BDCA3+) conventional DCs in huNSG mice. Furthermore, depletion of CD141+ DCs before stimulation significantly reduced IFN-α levels in vivo. This DC subset produced similar total amounts but different subtypes of IFN-α in response to synthetic double-stranded RNA compared with plasmacytoid DCs in response to a single-stranded RNA equivalent. Moreover, synthetic double-stranded RNA as adjuvant and antigen targeting to the endocytic receptor DEC-205, a combination that focuses antigen presentation for T-cell priming on CD141+ DCs, stimulated antigen-specific human CD4+ T-cell responses. Thus, the human CD141+ DC subset is a prominent source of IFN-α and interleukin-12 production and should be further evaluated for vaccine development.
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
authors.forename: Sonja
authors.initials: S
authors.lastname: Meixlsperger
authors.forename: Carol S
authors.initials: CS
authors.lastname: Leung
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Rämer
authors.forename: Maggi
authors.initials: M
authors.lastname: Pack
authors.forename: Liliana D
authors.initials: LD
authors.lastname: Vanoaica
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Breton
authors.forename: Steve
authors.initials: S
authors.lastname: Pascolo
authors.forename: Andres M
authors.initials: AM
authors.lastname: Salazar
authors.forename: Andrzej
authors.initials: A
authors.lastname: Dzionek
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schmitz
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D015778:Minor Histocompatibility Antigens; D012330:RNA, Double-Stranded / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C093569:DEC-205 receptor; D016898:Interferon-alpha; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface