Involvement of IL-6 in the anti-human immunodeficiency virus activity of IFN-tau in human macrophages.
IFN-tau is a non-cytotoxic type I IFN responsible for maternal recognition of the foetus in ruminants. IFN-tau has been found to inhibit HIV replication more strongly than human IFN-alpha, particularly in human monocyte-derived macrophages, without associated toxicity. Ovine IFN-tau uses the same anti-viral cellular pathways as human IFN-alpha in human macrophages, principally inhibiting the early steps of the biological cycle of HIV, preventing the integration of HIV DNA into the host-cell genome. In this study, we investigated the immunomodulatory properties of IFN-tau in human macrophages. We found that IFN-tau increased the production of IL-10 and IL-6, but not of IL-1beta or tumour necrosis factor alpha, in unstimulated, LPS-stimulated and HIV-1/Ba-L-infected macrophages. We also found that treatment with IL-6 inhibited HIV replication. Moreover, the neutralization of IL-6 activity in the cell culture supernatants of IFN-tau-treated macrophages led to a decrease in the anti-retroviral effects of IFN-tau, suggesting that IL-6 was involved in the anti-viral activity induced by IFN-tau. By focusing on the very early steps of the biological cycle of HIV, we showed that IL-6 co-operated with IFN-tau to decrease intracellular HIV RNA levels 2 h after infection.
Service de Neurovirologie, Commissariat à l'Energie Atomique, Université Paris-Sud, CRSSA, EPHE, IPSC, Fontenay-aux-Roses, France.
Christine
C
Rogez-Kreuz
Benjamin
B
Manéglier
Marc
M
Martin
Nathalie
N
Dereuddre-Bosquet
Jacques
J
Martal
Dominique
D
Dormont
Pascal
P
Clayette
D000818:Animals; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000821:virology; D011257:Pregnancy Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
D007155:Immunologic Factors; D007370:Interferon Type I; D007375:Interleukin-1; D015850:Interleukin-6; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C020947:interferon tau; D016753:Interleukin-10