Human Immunodeficiency Virus-1 Impairs IFN-Alpha Production Induced by TLR-7 Agonist in Plasmacytoid Dendritic Cells.
Plasmacytoid dendritic cells (pDCs) play an important role in innate immune response against viruses, mainly through interferon-α (IFN-α) secretion. Impaired IFN-α secretion has been observed in patients with acute human immunodeficiency virus type 1 (HIV-1) infection and the reasons for this impairment are still obscure. To know the grounds behind this situation, HIV-1 viral copy numbers similar to those found in primary HIV-1 infection were used to stimulate peripheral blood mononuclear cells (PBMCs) and pDCs in this study. Intracellular IFN-α production was seen as early as 2 h in pDCs with TLR-7 agonist (imiquimod) stimulation, but HIV-1 required 48 h to induce secretion of IFN-α in supernatants and it was 10 times less compared to imiquimod. Thus, it shows that HIV-1 delays and impairs IFN-α production from pDCs. Furthermore, the IFN-α inhibitory activity of HIV-1 was checked by stimulating PBMCs and pDCs with imiquimod either simultaneously with HIV-1 or after 2 h pre-exposure to HIV-1. Pre-exposure to HIV-1 resulted in significant reduction in IFN-α secretion by pDCs and PBMCs when compared to imiquimod alone. In addition, simultaneous stimulation of these populations with HIV-1 and imiquimod resulted in significant impairment in IFN-α production in pDCs but not in PBMCs. HIV-1 not only fails to induce IFN-α in adequate quantities but also inhibits IFN-α secretary capacity of pDCs. HIV-1 particles were found to bind CD303 receptor on pDC surface probably blocking initiation of cascade leading to IFN-α impairment. The understanding of the pathways that lead to this suppression may help in devising the HIV control strategies.
Department of Immunology, National AIDS Research Institute , Pune, India .
Ashwini
A
Dhamanage
Department of Immunology, National AIDS Research Institute , Pune, India .
Madhuri
M
Thakar
Department of Immunology, National AIDS Research Institute , Pune, India .
Ramesh
R
Paranjape
D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D006678:HIV / Q000276:immunology* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D016898:Interferon-alpha / Q000096:biosynthesis*; D051199:Toll-Like Receptor 7 / Q000819:agonists*
D016898:Interferon-alpha; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7
innate immunity; interferons