Plasmacytoid dendritic cell dynamics tune interferon-alfa production in SIV-infected cynomolgus macaques.

ABSTRACT: IFN-I production is a characteristic of HIV/SIV primary infections. However, acute IFN-I plasma concentrations rapidly decline thereafter. Plasmacytoid dendritic cells (pDC) are key players in this production but primary infection is associated with decreased responsiveness of pDC to TLR 7 and 9 triggering. IFN? production during primary SIV infection contrasts with increased pDC death, renewal and dysfunction. We investigated the contribution of pDC dynamics to both acute IFN? production and the rapid return of IFN? concentrations to pre-infection levels during acute-to-chronic transition. Nine cynomolgus macaques were infected with SIVmac251 and IFN?-producing cells were quantified and characterized. The plasma IFN-I peak was temporally associated with the presence of IFN?(+) pDC in tissues but IFN-I production was not detectable during the acute-to-chronic transition despite persistent immune activation. No IFN?(+) cells other than pDC were detected by intracellular staining. Blood-pDC and peripheral lymph node-pDC both lost IFN?(-) production ability in parallel. In blood, this phenomenon correlated with an increase in the counts of Ki67(+)-pDC precursors with no IFN? production ability. In tissues, it was associated with increase of both activated pDC and KI67(+)-pDC precursors, none of these being IFN?(+) in vivo. Our findings also indicate that activation/death-driven pDC renewal rapidly blunts acute IFN? production in vivo: pDC sub-populations with no IFN?-production ability rapidly increase and shrinkage of IFN? production thus involves both early pDC exhaustion, and increase of pDC precursors.

SUBMITTER: Bruel T 

PROVIDER: S-EPMC3907389 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature