Mezger Markus, Kneitz Susanne, Wozniok Iwona, Kurzai Oliver, Einsele Hermann, Loeffler Juergen
Medizinische Klinik und Poliklinik II, Würzburg, Germany.
J Infect Dis. 2008 Mar 15;197(6):924-31. doi: 10.1086/528694.
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).
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).
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.
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.
烟曲霉引起的侵袭性真菌感染对免疫功能低下的患者构成了巨大挑战。病原体检测由不同的受体介导，包括Toll样受体（TLR）、C型凝集素和五聚素。然而，关于它们对未成熟人类树突状细胞（iDC）的相关性知之甚少。
通过全基因组微阵列分析和实时聚合酶链反应研究iDC暴露于烟曲霉芽管后的基因表达模式。真菌受体通过短干扰RNA（siRNA）靶向，用于敲低TLR2、TLR4、DC-SIGN（树突状细胞特异性细胞间粘附分子3结合非整合素）、PTX3（五聚素相关基因）、dectin-1（C型凝集素结构域家族7成员A）和CARD9（半胱天冬酶募集结构域家族成员9）的表达。
暴露于烟曲霉诱导细胞因子、趋化因子、共刺激分子以及参与前列腺素合成的基因的表达，以及与真菌识别和吞噬相关的基因的表达。dectin-1的沉默导致促炎细胞因子（肿瘤坏死因子-α和白细胞介素-12）的表达降低，在暴露于烟曲霉、酵母聚糖或白色念珠菌之前用抗Dectin-1抗体处理也降低了促炎细胞因子的表达。
Dectin-1被确定为人类iDC上烟曲霉和白色念珠菌的重要受体，并被发现参与促炎细胞因子反应的诱导。
