title: Reciprocal regulation of plasmacytoid dendritic cells and monocytes during viral infection.
abstract: Reciprocal regulation of opposing functions characterizes biological systems. We now show that adenovirus-infected plasmacytoid dendritic cells (PDC) inhibit monocyte to myeloid dendritic cell (MDC) differentiation and function, and that adenovirus-infected monocytes inhibit PDC type I interferon secretion. Adenovirus-infected PDC secreted IFN-alpha, beta and omega in an 86:2:1 ratio. PDC type I interferons inhibited MDC differentiation and function (reduced IL-12 secretion, IFN-gamma induction, MLR and CD40 expression, and increased CD1a(+)CD14(+) cells). Type I interferon receptor blocking antibody reversed all PDC effects, and recombinant IFN-alpha, beta or omega replicated all effects, except reduced CD40. Adenovirus-infected monocytes suppressed PDC type I interferon secretion, which was reversed with anti-IL-10 neutralizing antibodies. Exogenous IL-10 suppressed PDC type I interferon secretion without reducing PDC viability. Therefore, monocyte IL-10 regulates PDC type I interferon secretion, and PDC type I interferons inhibit MDC differentiation and function. Such reciprocal regulation of potentially opposing influences may help modulate anti-pathogen immunity.
authors.affiliation: Tulane Medical School, New Orleans, LA 70112, USA. wzou@tulane.edu
authors.forename: W
authors.initials: W
authors.lastname: Zou
authors.forename: J
authors.initials: J
authors.lastname: Borvak
authors.forename: S
authors.initials: S
authors.lastname: Wei
authors.forename: T
authors.initials: T
authors.lastname: Isaeva
authors.forename: D T
authors.initials: DT
authors.lastname: Curiel
authors.forename: T J
authors.initials: TJ
authors.lastname: Curiel
mesh_terms: D000258:Adenovirus Infections, Human / Q000276:immunology*; D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007370:Interferon Type I / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*
chemical_list: D007370:Interferon Type I; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor