Flt3L-Mediated expansion of plasmacytoid dendritic cells suppresses HIV infection in humanized mice
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Cell reports ; vol. 29, no 9, p. 2770-2782.Éditeur·s
Cell PressAuteur·e·s
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Résumé·s
Plasmacytoid dendritic cells (plasmacytoid DC, pDC)
are major IFN-I producers and have been shown to be
affected by HIV through ill-defined mechanisms. In
this study, we directly assess the role of pDC in early
infection, evaluating whether modulating their abundance can alter viral replication. First, HIV infection
of humanized mice induces systemic depletion of
pDC, and in the presence of soluble FMS-like tyrosine
kinase 3 ligand (Flt3L), pDC levels remain elevated.
Flt3L significantly delays the onset of viremia and reduces viral replication via a process that is dependent
on pDC and mediated through an enhanced early
IFN-I response. pDC from Flt3L-treated mice are
more prone to express IFN-a following TLR7 stimulation, but this propensity is gradually decreased during
infection. In conclusion, maintaining pDC levels and
function is key to effective early viral control, and in
this context, these findings provide practical insights
for anti-HIV strategies and vaccine design.
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