HIV-1 and HIV-2 induce Interferon-lambda production by plasmacytoid Dendritic Cells

Abstract

Abstract Type III Interferons (IFN-λ) were barely studied during HIV infection, despite their antiviral properties similar to those of type I IFN and their important role during HCV infection, where IFN-λ3 gene polymorphisms correlate with viral clearance. We tested IFN-λ responses to HIV-1, and also to HIV-2, which is less pathogenic. We first stimulated PBMC (EFS-Inserm convention) enriched for dendritic cells (DC), the main IFN producers. Purified HIV-1 virions or H9 T cells chronically infected with HIV-1 induced transcription of IFN-λ1 and 2/3 mRNA (RT-qPCR), as well as the secretion of IFN-λ (ELISA). Similar results were obtained with HIV-2-infected cells or virions. Intracellular labeling for IFN-λ1 was detected by flow cytometry in BDCA-4+ plasmacytoid DC (pDC), but not in BDCA-1+ or -3+ conventional DC (cDC). This was confirmed in > 95% purified cell populations. Recognition of HIV-1 or HIV-2 by pDC induced their maturation (surface CD83 and CCR7 overexpression), and bystander maturation of cDC. Therefore, IFN-λ production by human blood pDC was induced at comparable levels by HIV-1 or HIV-2, either as cell-free viruses or as infected cells, indicating that it is not a clue for the difference in host-pathogen relationship between the two viruses, and that IFN-λ may contribute to the Interferon-Stimulated-Gene response during HIV infection. Knowledge of IFN-λ responses to HIV will help modulating IFN responses toward viral control and against pathogenic immune hyperactivation.