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In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 16, 2013
Human immunodeficiency virus gp120 inhibits interleukin-12 secretion by human monocytes: an indirect
1Laboratoire Virus, Neurones et Immunité, Université Paris-Sud, Le Kremlin-Bicêtre, France.
Insights
Human immunodeficiency virus (HIV) gp120 protein impairs interleukin-10 (IL-10) and interleukin-12 (IL-12) production in monocytes and macrophages. This immune disregulation, driven by IL-10, may affect the immune response during HIV infection.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Interleukin-12 (IL-12) is a cytokine produced by monocytes and macrophages with crucial immunomodulatory functions.
- Understanding how viral infections impact cytokine production is vital for immune response modulation.
Purpose of the Study:
- To investigate the effect of human immunodeficiency virus (HIV) gp120 on IL-12 production in monocytes and macrophages.
- To elucidate the role of IL-10 in mediating potential gp120-induced immune dysregulation.
Main Methods:
- Human monocytes and macrophages were preincubated with HIV-gp120.
- Expression of IL-12 mRNA and protein levels was assessed following stimulation with Staphylococcus aureus strain cowan I (SAC).
- Interleukin-10 (IL-10) synthesis was measured in response to HIV-gp120.
Main Results:
- HIV-gp120 significantly decreased IL-12 mRNA subunit expression and protein production (p40 and p70) in monocytes and macrophages stimulated with SAC.
- HIV-gp120 induced significant IL-10 synthesis in human monocyte cultures.
- IL-10 was identified as the mediator inhibiting IL-12 mRNA accumulation and protein secretion.
Conclusions:
- HIV-gp120 induces IL-10 production in monocytes and macrophages.
- This IL-10 production leads to the suppression of IL-12 expression and secretion.
- The resulting IL-10/IL-12 disregulation in uninfected cells may contribute to altered immune responses during HIV infection.
Abstract:
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.
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