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Published on: June 19, 2013
Production of interferon-alpha/beta by murine dendritic cell lines stimulated by virus and bacteria
M L Eloranta1, K Sandberg, P Ricciardi-Castagnoli
1Department of Veterinary Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Insights
Murine dendritic cell (DC) lines D2SC/1 and FSDC show distinct interferon-alpha/beta (IFN-alpha/beta) production capabilities. Priming DCs with specific cytokines modulates their IFN-alpha/beta response to viral and bacterial stimuli.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Dendritic cells (DCs) are crucial immune regulators.
- Interferon-alpha/beta (IFN-alpha/beta) plays a key role in innate immunity.
- Understanding DC responses to pathogens is vital for immune modulation.
Purpose of the Study:
- To investigate the IFN-alpha/beta production capacity of two murine DC lines: D2SC/1 and FSDC.
- To explore the effects of priming with various cytokines on DC IFN-alpha/beta responses.
- To elucidate differential induction mechanisms of IFN-alpha/beta by different stimuli.
Main Methods:
- Stimulation of DC lines (D2SC/1 and FSDC) with herpes simplex virus (HSV), Sendai virus (SV), Escherichia coli, and Staphylococcus aureus Cowan I.
- Priming of DC lines with recombinant IFN-beta, granulocyte-macrophage colony-stimulating factor, IFN-gamma, tumor necrosis factor-alpha, IL-10, and IL-4.
- Quantification of IFN-alpha/beta production and analysis of response kinetics.
Main Results:
- D2SC/1 cells produced both IFN-alpha and -beta in response to viral and bacterial stimuli.
- FSDC cells predominantly produced IFN-beta and showed limited response to bacteria.
- Priming with IFN-beta/granulocyte-macrophage colony-stimulating factor enhanced IFN-alpha/beta production in D2SC/1 cells for certain stimuli, while IFN-gamma was most effective for FSDC cells.
- Different kinetics of IFN-alpha/beta response suggest distinct induction pathways for SV versus HSV and bacteria.
Conclusions:
- The studied DC lines offer a valuable model for investigating IFN-alpha/beta induction and regulation.
- DC-derived IFN-alpha/beta has significant immunoregulatory functions.
- Cytokine priming differentially impacts DC IFN-alpha/beta production, highlighting specific signaling pathways.
Abstract:
The interferon-alpha and -beta (IFN-alpha/beta) producing ability of the two murine dendritic cell (DC) lines D2SC/1 and FSDC was studied. The D2SC/1 cells produced IFN-alpha and -beta when stimulated by herpes simplex virus (HSV), Sendai virus (SV) or by the bacteria Escherichia coli or Staphylococcus aureus Cowan I. Precultivating (priming) D2SC/1 cells with recombinant IFN-beta or a combination of IFN-beta and granulocyte-macrophage colony-stimulating factor increased production of IFN-alpha/beta induced by HSV or the bacteria, but not by SV. Also, the kinetics of IFN-alpha/beta responses were different for SV compared to HSV and the bacteria, suggesting different induction mechanisms. The FSDC cells differed from the D2SC/1 cells mainly in that predominantly IFN-beta was produced, that little or no IFN-alpha/beta production was induced by the bacteria, and that the IFN-alpha/beta responses were most efficiently primed by IFN-gamma. Priming the DC lines with tumour necrosis factor-alpha, interleukin-10 (IL-10) or IL-4 did not affect the IFN-alpha/beta response induced by HSV. The results show that the two DC lines provide a convenient tool to study the induction and control of the IFN-alpha/beta response, as well as the immunoregulatory role of IFN-alpha/beta produced by DC.
