title: CD11c+ dendritic cells and plasmacytoid DCs are activated by human cytomegalovirus and retain efficient T cell-stimulatory capability upon infection.
abstract: It has been suggested that human cytomegalovirus (HCMV) evades the immune system by infecting and paralyzing antigen-presenting cells. This view is based mainly on studies of dendritic cells (DCs) obtained after culture of monocytes (moDCs). It is contradicted by the asymptomatic course of HCMV infection in healthy persons, indicating that other key antigen-presenting cells induce an efficient immune response. Here we show that HCMV activates CD11c+ DCs and plasmacytoid DCs (PDCs). In contrast to moDCs, CD11c+ DCs and PDCs produced interferon (IFN) type 1 when exposed to HCMV. Autocrine IFN type 1 partially protected CD11c+ DCs against infection, whereas PDCs were resistant to HCMV even when IFN type 1 activity was inhibited. HCMV exposure induced the maturation of CD11c+ DCs by IFN type 1-dependent and -independent mechanisms. Importantly, CD11c+ DCs infected by inhibiting IFN type 1 activity retained full capacity to stimulate T cells. Renal transplant recipients receiving immunosuppressive treatment had lower frequencies of CD11c+ DCs and PDCs in blood than did healthy controls. The results show that HCMV activates the immune system by interacting with CD11c+ DCs and PDCs and that recipients of renal transplants have low frequencies of these cell types in blood.
authors.affiliation: Institute of Immunology, Oslo, Norway.
authors.forename: Espen Ø
authors.initials: EØ
authors.lastname: Kvale
authors.forename: Jakob
authors.initials: J
authors.lastname: Dalgaard
authors.forename: Fridtjof
authors.initials: F
authors.lastname: Lund-Johansen
authors.forename: Halvor
authors.initials: H
authors.lastname: Rollag
authors.forename: Lorant
authors.initials: L
authors.lastname: Farkas
authors.forename: Karsten
authors.initials: K
authors.lastname: Midtvedt
authors.forename: Frode L
authors.initials: FL
authors.lastname: Jahnsen
authors.forename: Jan E
authors.initials: JE
authors.lastname: Brinchmann
authors.forename: Johanna
authors.initials: J
authors.lastname: Olweus
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D019898:Autocrine Communication / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D016030:Kidney Transplantation; D008213:Lymphocyte Activation / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D039521:CD11c Antigen; D007370:Interferon Type I