Reciprocal regulation of plasmacytoid dendritic cells and monocytes during viral infection

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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‐α, β and ω in an 86:2:1 ratio. PDC type I interferons inhibited MDC differentiation and function (reduced IL‐12 secretion, IFN‐γ induction, MLR and CD40 expression, and increased CD1a+CD14+ cells). Type I interferon receptor blocking antibody reversed all PDC effects, and recombinant IFN‐α, β or ω 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.

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