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Production by Plasmacytoid Dendritic Cells Exerts an Antiviral Effect on Thymic HIV-1 Infection1
,
,
Departments of
*
Microbiology, Immunology, and Molecular Genetics and
Pediatrics,
University of California Los Angeles AIDS Institute, and
Jonsson Comprehensive Cancer Center, David E. Geffen School of Medicine, University of California, Los Angeles CA 90095; and
¶
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Plasmacytoid dendritic cells (pDC) are the principal producers of IFN-
in response to viral infection. Because pDC are present in the thymus, we investigated the consequences of HIV-1-induced IFN- production by thymic pDC. We observed that thymic pDC as well as thymocytes express intracellular IFN- 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- in response to CpG oligonucleotides, consistent with the observations of others that peripheral pDC produce IFN- upon engagement of TLR-9. Importantly, CpG considerably increased IFN- 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-. The degree of inhibition depends on the level of IFN- produced by the thymic pDC.
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