Interactions between dendritic cells and viruses

We provide phenotypic and functional evidence of monocytoid and plasmacytoid dendritic cells (DCs) in blood and bone marrow of SIV− and SIV+ rhesus macaques (RMs) and SIV− and SIV+ sooty mangabeys (SMs). To mobilize DC subsets, a fms-like tyrosine kinase (flt3L)-IgG2 fusion protein was administered (100 μg/kg subcutaneously) for 5 days. The DC subsets were identified within the lineage (LIN−) major histocompatibility complex (MHC) Class II + fraction. The monocytoid and plasmacytoid DCs were characterized as CD11c+ CD123− and CD11c− CD123+, respectively. Mobilization of both CD11c + and CD123+ DCs occurred following flt3 L-IgG2 administration. In SIV− RMs, SIV+ RMs, SIV− SMs and SIV+ SMs the mobilized DCs had an immature phenotype (low expression of CCR7 and CD80). Following Flu stimulation, plasmacytoid DCs from RMs and SMs secreted increased levels of interferon-α (IFNα). Interestingly, not all plasmacytoid DCs responded to CpG stimulation. SIV + RM, SIV− SM and SIV+ SM CD123 + DCs did not secrete IFNα following CpG stimulation. Corresponding DC subsets were identified by flow cytometry analyses in the bone marrow (BM). In the BM, there was an expansion of LIN− MHC Class II + cells in both SMs and RMs following flt3L-IgG2 mobilization. The CD11c+ and CD123+ DCs present in the BM had an immature phenotype (low expression of CD80 and CCR7 on DCs). There was also no effect of DC mobilization in the viral load of SIV+ infected animals. We have identified two distinct DC subsets in SMs and RMs that resemble human DCs. In addition, it was possible to mobilize DCs in SIV + monkeys. The characterization of the DC subsets will increase our understanding of DC biology and possibly lead to new HIV therapeutics.