title: Enterovirus-infected β-cells induce distinct response patterns in BDCA1+ and BDCA3+ human dendritic cells.
abstract: Enteroviruses often cause mild disease, yet are also linked to development of autoimmune diabetes. Dendritic cells (DCs) shape both innate and adaptive immune responses, including anti-viral responses. How different human DC subsets shape anti-viral responses, whether they have complementary or overlapping functions and how this relates to autoimmune responses is largely unknown. We used enterovirus-infected β-cells and freshly isolated human myeloid DC (mDC) subsets as a model for autoimmune type 1 diabetes. Our data show that both the BDCA1+ and BDCA3+ mDC subsets engulf mock- as well as virus-infected β-cells, albeit BDCA1+ mDCs are more efficient. Uptake of enterovirus-infected, but not mock-infected cells, activated both DC subsets as indicated by the induction of co-stimulatory molecules and secretion of type I and type III interferons. Both subsets produced similar amounts of interferon-α, yet the BDCA3+ DC were superior in IFN-λ production. The BDCA1+ mDCs more strongly upregulated PD-L1, and were superior in IL-12 and IL-10 production as compared to the BDCA3+ DC. Despite lack of IL-12 production by the BDCA3+ DC, both BDCA1+ and BDCA3+ DCs activated T cells in allogeneic mixed lymphocyte reaction towards a Th1-type reactivity while suppressing Th2-associated cytokines.
authors: Department of Tumor Immunology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors: Barbara M
authors: BM
authors: Schulte
authors: Department of Tumor Immunology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors: Paul R
authors: PR
authors: Gielen
authors: Department of Tumor Immunology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors: Esther D
authors: ED
authors: Kers-Rebel
authors: Department of Tumor Immunology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors: Gerty
authors: G
authors: Schreibelt
authors: Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors: Frank J M
authors: FJ
authors: van Kuppeveld
authors: Department of Tumor Immunology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors: Gosse J
authors: GJ
authors: Adema
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004770:Enterovirus / Q000276:immunology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D051381:Rats
chemical_list: D016207:Cytokines