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Updated: Aug 9, 2026
Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.
Published on: September 1, 2015
Involvement of dihydropyridine-sensitive calcium channels in human dendritic cell function. Competition by HIV-1 Tat
A Poggi1, A Rubartelli, M R Zocchi
1Laboratory of Immunopathology, National Institute for Cancer Research and Advanced Biotechnology Center, Genoa 16132, Italy.
Insights
Human dendritic cells use calcium channels for key immune functions. HIV Tat protein blocks these channels, inhibiting dendritic cell activity and potentially impacting immune responses.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Extracellular calcium entry regulates leukocyte functions, but mechanisms in dendritic cells are unclear.
- Dendritic cells are crucial for initiating immune responses.
- Calcium influx is vital for specific dendritic cell functions.
Purpose of the Study:
- To investigate the role of calcium channels in human dendritic cell function.
- To determine the effect of human immunodeficiency virus type 1 Tat protein on dendritic cells.
- To elucidate the molecular mechanisms by which Tat affects dendritic cells.
Main Methods:
- Phenotypical and biochemical analysis of peripheral blood-derived human dendritic cells.
- Assessment of dendritic cell functions including apoptotic body engulfment and IL-12 production.
- Use of dihydropyridine drugs (nifedipine, Bay K 8644) and HIV-1 Tat protein.
Main Results:
- Human dendritic cells express dihydropyridine-sensitive calcium channels.
- Nifedipine blocked calcium influx, inhibiting dendritic cell functions.
- HIV-1 Tat inhibited dendritic cell functions by blocking extracellular calcium influx.
- Bay K 8644 reversed Tat's inhibition, implicating L-type calcium channels.
- Tat and dihydropyridine drugs competed for binding to dendritic cells.
Conclusions:
- Dendritic cells utilize dihydropyridine-sensitive L-type calcium channels for critical functions.
- HIV-1 Tat inhibits dendritic cell functions by targeting these L-type calcium channels.
- These findings reveal a mechanism for HIV-1 Tat's immunomodulatory effects on dendritic cells.
Abstract:
The entry of extracellular calcium in leukocytes mediates several cellular processes; however, unlike in excitable tissues, the underlying molecular mechanisms are poorly defined. In this paper we provide phenotypical and biochemical evidence that peripheral blood-derived human dendritic cells express dihydropyridine-sensitive calcium channels. Exposure to the dihydropyridine drug nifedipine, which binds L-type calcium channels blocking calcium influx, prevents two dendritic cell functions that are dependent on extracellular calcium entry: apoptotic body engulfment and interleukin-12 production induced by cross-linking of the surface lectin NKRP1A. It is known that exogenous human immunodeficiency virus, type 1 Tat affects several Ca2+-dependent immune cell responses. Here we demonstrate that Tat inhibits apoptotic body engulfment and interleukin-12 production by blocking extracellular calcium influx. This inhibition is prevented by the calcium channel agonist dihydropyridine derivative Bay K 8644, suggesting the involvement of L-type calcium channels. This hypothesis is further supported by the observation that Tat and dihydropyridine drugs compete for binding to dendritic cells. Taken together, these findings indicate that exogenous Tat exerts its inhibitory effects on dendritic cells by blocking dihydropyridine-sensitive L-type calcium channels.
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