Maturation inside and outside bone marrow dendritic cells (BMDCs) modulated by interferon-α (IFN-α)

Abstract

Interferons are made by cells in response to appropriate stimuli such as viruses, bacteria, parasites or tumor cells and are released into the surrounding medium. They then bind to receptors on target cells to allow for communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors. IFN-α is produced by leukocytes and is mainly involved in innate immune response against viral or bacterial infections and for tumor control. The aim of this work is to explore the detailed modulation of IFN-α on phenotypic and functional maturation inside and outside murine bone marrow derived dendritic cells (BMDCs). The maturity of BMDCs post treatment with IFN-α was evaluated with conventional light microscope and transmission electron microscopy (TEM) for morphology changes; flow cytometry (FCM) for changes of surface molecules on BMDCs; cytochemistry, acid phosphatase activity (ACP) test, and FITC-dextran bio-assay for biochemistry analysis and enzyme-linked immunosorbent assay (ELISA) for cytokine production by BMDCs. We have shown that IFN-α 1) up-regulates the expression of MHC II, CD40, CD83, CD80 and CD86 molecules on BMDCs; 2) down-regulates the rates of pinocytosis and phagocytosis by BMDCs as evidenced by the results of decreased ACP, and FITC-dextran bio-assay; 3) enhances the ability of BMDCs to drive T cell function; and 4) induces higher levels of IL-12 and TNF-α secreted by BMDCs. Therefore, we conclude that IFN-α can efficiently promote the maturation of BMDCs through detailed modulation inside and outside BMDCs. Our study has provided more detailed data on changes of BMDCs modulated by IFN-α, and rationale on future application of IFN-α for enhancing host immunity and potent adjuvant administration in the design of DC-based vaccines.