Plasmacytoid dendritic cell dynamics tune interferon-alfa production in SIV-infected cynomolgus macaques.
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. IFNα production during primary SIV infection contrasts with increased pDC death, renewal and dysfunction. We investigated the contribution of pDC dynamics to both acute IFNα production and the rapid return of IFNα concentrations to pre-infection levels during acute-to-chronic transition. Nine cynomolgus macaques were infected with SIVmac251 and IFNα-producing cells were quantified and characterized. The plasma IFN-I peak was temporally associated with the presence of IFNα(+) pDC in tissues but IFN-I production was not detectable during the acute-to-chronic transition despite persistent immune activation. No IFNα(+) cells other than pDC were detected by intracellular staining. Blood-pDC and peripheral lymph node-pDC both lost IFNα(-) production ability in parallel. In blood, this phenomenon correlated with an increase in the counts of Ki67(+)-pDC precursors with no IFNα production ability. In tissues, it was associated with increase of both activated pDC and KI67(+)-pDC precursors, none of these being IFNα(+) in vivo. Our findings also indicate that activation/death-driven pDC renewal rapidly blunts acute IFNα production in vivo: pDC sub-populations with no IFNα-production ability rapidly increase and shrinkage of IFNα production thus involves both early pDC exhaustion, and increase of pDC precursors.
Division of Immuno-Virology, Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France ; Unité Mixte de Recherche UMR-E01, Université Paris-Sud, Orsay, France.
Timothée
T
Bruel
Division of Immuno-Virology, Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France ; Unité Mixte de Recherche UMR-E01, Université Paris-Sud, Orsay, France.
Stéphanie
S
Dupuy
Division of Immuno-Virology, Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France ; Unité Mixte de Recherche UMR-E01, Université Paris-Sud, Orsay, France.
Thomas
T
Démoulins
Neurovirology Laboratory, Bertin Pharma, Fontenay-aux-Roses, France.
Christine
C
Rogez-Kreuz
Université Paris Descartes, Sorbonne Paris Cité, Paris, France ; INSERM, U1016, Institut Cochin, Paris, France ; CNRS, UMR8104, Paris, France ; Université Paris Diderot, Paris, France.
Jacques
J
Dutrieux
Division of Immuno-Virology, Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France.
Aurélien
A
Corneau
Division of Immuno-Virology, Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France ; Unité Mixte de Recherche UMR-E01, Université Paris-Sud, Orsay, France.
Antonio
A
Cosma
INSERM, U1016, Institut Cochin, Paris, France ; CNRS, UMR8104, Paris, France ; Université Paris Diderot, Paris, France.
Rémi
R
Cheynier
Division of Immuno-Virology, Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France ; Unité Mixte de Recherche UMR-E01, Université Paris-Sud, Orsay, France.
Nathalie
N
Dereuddre-Bosquet
Division of Immuno-Virology, Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France ; Unité Mixte de Recherche UMR-E01, Université Paris-Sud, Orsay, France.
Roger
R
Le Grand
Division of Immuno-Virology, Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France ; Unité Mixte de Recherche UMR-E01, Université Paris-Sud, Orsay, France.
Bruno
B
Vaslin
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D016898:Interferon-alpha / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008252:Macaca fascicularis; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology
D016898:Interferon-alpha; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9