H-ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses
H-ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses
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DOI：
10.1111/imm.12501
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发表时间：
2015-10-01
期刊：
影响因子：
6.4
通讯作者：
Schelenz, Silke
中科院分区：
文献类型：
--
作者：
Bidula, Stefan;Sexton, Darren W.;Schelenz, Silke
烟曲霉是一种机会性真菌病原体，通常感染免疫功能低下患者的肺部，导致高死亡率。H-Ficolin是一种先天免疫调理素，由II型肺泡上皮细胞产生，可参与肺部防御感染。在这里，我们使用人类II型肺泡上皮细胞系A549来确定H-ficolin在真菌防御中的作用。此外，我们调查了肺移植患者肺炎期间支气管肺泡灌洗液中H-ficolin的存在。H-Ficolin通过L-聚焦、d -甘露糖和n -乙酰氨基葡萄糖残基以钙和ph依赖的方式与烟曲霉分生孢子结合。此外，识别导致凝集素补体途径激活并增强真菌与A549细胞的关联。识别后，H-ficolin活化表现为A549细胞中白细胞介素-8的产生增加，这涉及细胞内信号通路的激活，包括丝裂原活化蛋白激酶MAPK激酶1/2、p38 MAPK和c-Jun n末端激酶。最后，肺部感染患者支气管肺泡灌洗液中H-ficolin浓度显著高于对照组（n = 16; P = 0.00726）。受试者工作特征曲线分析进一步强调了H-ficolin作为肺部感染诊断标志物的潜力（曲线下面积= 0.77;P < 0.0001）。因此，H-ficolin通过激活凝集素补体途径，增强真菌-宿主相互作用和调节免疫反应参与烟曲霉的防御。
Aspergillus fumigatus is an opportunistic fungal pathogen that typically infects the lungs of immunocompromised patients leading to a high mortality. H-Ficolin, an innate immune opsonin, is produced by type II alveolar epithelial cells and could participate in lung defences against infections. Here, we used the human type II alveolar epithelial cell line, A549, to determine the involvement of H-ficolin in fungal defence. Additionally, we investigated the presence of H-ficolin in bronchoalveolar lavage fluid from transplant patients during pneumonia. H-Ficolin exhibited demonstrable binding to A. fumigatus conidia via L-fucose, D-mannose and N-acetylglucosamine residues in a calcium-and pH-dependent manner. Moreover, recognition led to lectin complement pathway activation and enhanced fungal association with A549 cells. Following recognition, H-ficolin opsonization manifested an increase in interleukin-8 production from A549 cells, which involved activation of the intracellular signalling pathways mitogen-activated protein kinase MAPK kinase 1/2, p38 MAPK and c-Jun N-terminal kinase. Finally, H-ficolin concentrations were significantly higher in bronchoalveolar lavage fluid of patients with lung infections compared with control subjects (n = 16; P = 0.00726). Receiver operating characteristics curve analysis further highlighted the potential of H-ficolin as a diagnostic marker for lung infection (area under the curve = 0.77; P < 0.0001). Hence, H-ficolin participates in A. fumigatus defence through the activation of the lectin complement pathway, enhanced fungus-host interactions and modulated immune responses.