The Effects of Fungi on the Activation of Monocyte Derived Dendritic Cells and Its Impact on Priming Th Polarization

ABSTRACT

BACKGROUND AND OBJECTIVES: The mucosal immune response depends on the surveillance network established by dendritic cells (DC) localized within the respiratory epithelium. Fungi have been increasingly recognized as important pathogens in respiratory diseases. We hypothesized that DCs play a central role in the immune response against airborne fungi. MATERIALS AND METHODS: Monocyte-derived DCs were developed by incubating monocytes with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor. DCs were stimulated with Alternaria alternata and Aspergillus nigra for 24 hours and then co-cultured with CD4-positive lymphocytes for 6 days. Levels of IL-6 and tumor necrosis factor-alpha (TNF-alpha) were measured to determine activation of the DCs, and levels of TNF-alpha, IL-5, and interferon-gamma (INF-gamma) were measured to determine Th polarization. DC migration was induced with conditioned media from nasal polyp epithelial cells stimulated with fungi. RESULTS: Alternaria and Aspergillus activated DCs with enhanced production of cytokines. When activated DCs were co-cultured with CD4-positive lymphocytes, Th2 cytokine and IL-5 production was significantly increased by Alternaria. DC migration was significantly increased by conditioned media from cells that were activated with Alternaria. CONCLUSION: Airborne fungi induced different immune responses depending on the fungi. Alternaria strongly induced DC migration and a Th2 immune response.