Human immunodeficiency virus gp120 inhibits interleukin-12 secretion by human monocytes: an indirect interleukin-10-mediated effect.
Interleukin-12 (IL-12), a cytokine with in vitro and in vivo immunomodulatory effects, is produced mostly by activated monocytes and macrophages. To study the effect of human immunodeficiency virus (HIV) infection on IL-12 production, we investigated the expression of IL-12 at mRNA and protein levels by human monocytes preincubated with HIV-gp120. In these conditions, we show that monocytes have a decreased ability to express IL-12 mRNA subunits and to produce IL-12 p40 and bioactive p70 proteins in response to Staphylococcus aureus strain cowan I (SAC). We showed that in human monocyte cultures, HIV-gp120 induces a significant IL-10 synthesis, which in turn inhibits IL-12 subunits mRNA accumulation and protein secretion after SAC-activation. Similar data were obtained with human macrophages. These results suggest that, during HIV infection, gp120 induces in uninfected monocytes and macrophages IL-10/IL-12 disregulation, which can alter immune response.
Taoufik
Y
Y
Laboratoire Virus, Neurones et Immunité, Université Paris-Sud, Le Kremlin-Bicêtre, France.
Lantz
O
O
Wallon
C
C
Charles
A
A
Dussaix
E
E
Delfraissy
J F
JF
D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis
D015699:HIV Envelope Protein gp120; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12