Inhibitory effects of human immunodeficiency virus gp120 and Tat on CpG-A-induced inflammatory cytokines in plasmacytoid dendritic cells.
Plasmacytoid dendritic cells (pDCs), not only inhibit viral replication, but also play an essential role in linking the innate and adaptive immune system. In this study, we explored the effects of human immunodeficiency virus (HIV) gp120 and tat on CpG-A-induced inflammatory cytokines in pDCs. The results provided fundamental insights into HIV pathogenesis that may hold promise for preventative and even curative strategies. pDCs were isolated using blood DC antigen 4 (BDCA-4) DC isolation kit, and the purity was analyzed using BDCA-2 antibody by flow cytometry. pDCs and peripheral blood mononuclear cells (PBMCs) were stimulated by either CpG-A (5 µg/ml), gp120 (0.5 µg/ml), tat (0.5 µg/ml), or CpG-A treatment combined with gp120 or tat. The production of type I interferons (IFNs) and other inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interlukine-6 (IL-6), and interferon-gamma-inducible protein-10 (IP-10) in the culture supernatant, was determined by enzyme-linked immunosorbent assay. The results showed that CpG-A induced high levels of type I IFNs and other inflammatory cytokines, including TNF-α, IL-6, and IP-10, in pDCs. Concomitant treatment with gp120 reduced the levels of IFN-α, IFN-β, TNF-α, IL-6, and IP-10 induced by CpG-A in pDCs by 79%, 53%, 60%, 50%, and 34%, respectively, while tat suppressed them by 88%, 66%, 71%, 64%, and 53%, respectively. Similar results were demonstrated in CpG-A-treated PBMCs. In conclusion, gp120 and tat are effective inhibitors of the CpG-A-mediated induction of type I IFNs and other inflammatory cytokines from pDCs and PBMCs.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,  Institute of Infectious Diseases,  the First Affiliated Hospital,  Zhejiang University School of Medicine, Hangzhou 310003,  China.
Meixin
M
Fang
Ning
N
Xu
Xueting
X
Shao
Jin
J
Yang
Nanping
N
Wu
Hangping
H
Yao
D000954:Antigens, Surface / Q000378:metabolism; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000494:pharmacology*
D000954:Antigens, Surface; C443299:CLEC4C protein, human; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines; D015699:HIV Envelope Protein gp120; D018836:Inflammation Mediators; D016898:Interferon-alpha; D015850:Interleukin-6; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C478196:blood dendritic cell antigen 4, human; D054322:tat Gene Products, Human Immunodeficiency Virus; D016899:Interferon-beta