The Serum Opsonin L-ficolin Is Detected in Lungs of Human Transplant Recipients Following Fungal Infections and Modulates Inflammation and Killing of Aspergillus fumigatus
The Serum Opsonin L-ficolin Is Detected in Lungs of Human Transplant Recipients Following Fungal Infections and Modulates Inflammation and Killing of Aspergillus fumigatus
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DOI：
10.1093/infdis/jiv027
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发表时间：
2015-07-15
影响因子：
6.4
通讯作者：
Schelenz, Silke
中科院分区：
文献类型：
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作者：
Bidula, Stefan;Sexton, Darren W.;Schelenz, Silke
背景。侵袭性曲霉病 (IA) 是一种由烟曲霉引起的免疫功能低下个体危及生命的全身性真菌感染。已观察到人血清调理素 L-ficolin 可识别烟曲霉并参与真菌防御。方法。使用肺上皮细胞、原代人单核细胞源性巨噬细胞 (MDM) 和来自健康供体的中性粒细胞，我们通过流式细胞术和显微镜评估了 L-ficolin 调理过的活烟曲霉分生孢子的吞噬作用和杀灭作用。此外，通过细胞计数珠阵列测量细胞因子，并通过酶联免疫吸附测定测量来自肺移植受者的支气管肺泡灌洗（BAL）液中的L-ficolin。结果。 L-ficolin 调理作用可增加分生孢子的摄取并增强 MDM 和中性粒细胞对烟曲霉的杀灭作用。感染后 24 小时，调理作用还显示 A549 肺上皮细胞释放的白细胞介素 8 增加，但 MDM 和中性粒细胞释放的白细胞介素 1β、白细胞介素 6、白细胞介素 8、白细胞介素 10 和肿瘤坏死因子 α 减少。真菌感染患者 BAL 液中 L-ficolin 的浓度显着高于对照受试者 (P = .00087)，并且接受操作特征曲线分析强调了 L-ficolin 对肺部感染的诊断潜力（曲线下面积，0.842；P < .0001）。结论。 L-ficolin 调节对烟曲霉的免疫反应。此外，L-ficolin 首次被证明存在于人类肺部。
Background. Invasive aspergillosis (IA) is a life-threatening systemic fungal infection in immunocompromised individuals that is caused by Aspergillus fumigatus. The human serum opsonin, L-ficolin, has been observed to recognize A. fumigatus and could participate in fungal defense.Methods. Using lung epithelial cells, primary human monocyte-derived macrophages (MDMs), and neutrophils from healthy donors, we assessed phagocytosis and killing of L-ficolin-opsonized live A. fumigatus conidia by flow cytometry and microscopy. Additionally, cytokines were measured by cytometric bead array, and L-ficolin was measured in bronchoalveolar lavage (BAL) fluid from lung transplant recipients by enzyme-linked immunosorbent assay.Results. L-ficolin opsonization increased conidial uptake and enhanced killing of A. fumigatus by MDMs and neutrophils. Opsonization was also shown to manifest an increase in interleukin 8 release from A549 lung epithelial cells but decreased interleukin 1 beta, interleukin 6, interleukin 8, interleukin 10, and tumor necrosis factor alpha release from MDMs and neutrophils 24 hours after infection. The concentration of L-ficolin in BAL fluid from patients with fungal infection was significantly higher than that for control subjects (P = .00087), and receiving operating characteristic curve analysis highlighted the diagnostic potential of L-ficolin for lung infection (area under the curve, 0.842; P < .0001).Conclusions. L-ficolin modulates the immune response to A. fumigatus. Additionally, for the first time, L-ficolin has been demonstrated to be present in human lungs.