Endogenous IFN-α Production by Plasmacytoid Dendritic Cells Exerts an Antiviral Effect on Thymic HIV-1 Infection

Abstract

Plasmacytoid dendritic cells (pDC) are the principal producers of IFN-α in response to viral infection. Because pDC are present in the thymus, we investigated the consequences of HIV-1-induced IFN-α production by thymic pDC. We observed that thymic pDC as well as thymocytes express intracellular IFN-α upon infection with HIV-1. However, only the pDC could suppress HIV-1 replication, because depletion of pDC resulted in enhancement of HIV-1 replication in thymocytes. Thymic pDC could also produce IFN-α in response to CpG oligonucleotides, consistent with the observations of others that peripheral pDC produce IFN-α upon engagement of TLR-9. Importantly, CpG considerably increased IFN-α production induced by HIV-1, and addition of CpG during HIV-1 infection enhanced expression of the IFN response protein MxA in thymocytes and strongly reduced HIV-replication. Our data indicate that thymic pDC modulate HIV-1 replication through secretion of IFN-α. The degree of inhibition depends on the level of IFN-α produced by the thymic pDC.