Proinflammatory Response of Immature Human Dendritic Cells is Mediated by Dectin‐1 after Exposure to<i>Aspergillus fumigatus</i>Germ Tubes

Abstract

BACKGROUND: Invasive fungal infections caused by Aspergillus fumigatus represent a great challenge for immunocompromised patients. Pathogen detection is mediated by different receptors, including Toll-like receptors (TLRs), C-type lectins, and pentraxines. However, little is known about their relevance for immature human dendritic cells (iDCs). METHODS: The gene expression pattern of iDCs after exposure to A. fumigatus germ tubes was studied by use of whole genome microarray analysis and real-time polymerase chain reaction. Fungal receptors were targeted by means of short interfering RNAs (siRNAs), which were used to knock down expression of TLR2, TLR4, DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), PTX3 (pentraxin-related gene), dectin-1 (C-type lectin domain family 7, member A), and CARD9 (caspase recruitment domain family, member 9). RESULTS: Exposure to A. fumigatus induced expression of cytokines, chemokines, costimulatory molecules, and genes involved in prostaglandin synthesis, as well as genes related to fungal recognition and phagocytosis. Silencing of dectin-1 resulted in reduced expression of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-12), which was also reduced by anti-Dectin-1 antibody treatment prior to exposure to A. fumigatus, zymosan, or Candida albicans. CONCLUSION: Dectin-1 was identified as an important receptor for A. fumigatus and C. albicans on human iDCs and was found to be involved in the induction of a proinflammatory cytokine response.