Human Natural Killer Cells Exhibit Direct Activity Against Aspergillus fumigatus Hyphae, But Not Against Resting Conidia
Human Natural Killer Cells Exhibit Direct Activity Against Aspergillus fumigatus Hyphae, But Not Against Resting Conidia
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DOI：
10.1093/infdis/jiq062
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发表时间：
2011-02-01
影响因子：
6.4
通讯作者：
Lehrnbecher, Thomas
中科院分区：
文献类型：
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作者：
Schmidt, Stanislaw;Tramsen, Lars;Lehrnbecher, Thomas
由于自然杀伤 (NK) 细胞可以杀死肿瘤细胞并对抗感染，因此人们越来越关注将 NK 细胞过继转移至造血干细胞受体。不幸的是，在人类中，NK 细胞针对曲霉属物种的活性知之甚少，而曲霉属物种是干细胞受体中侵袭性真菌感染的主要原因。我们的结果表明，未刺激和白介素 2 预刺激的人类 NK 细胞可杀死烟曲霉菌丝，但不影响静止的分生孢子。预刺激的 NK 细胞上清液和人穿孔素也可诱导杀伤。曲霉菌显着降低了预刺激 NK 细胞产生的高水平干扰素-γ和粒细胞巨噬细胞集落刺激因子，表明该真菌具有免疫抑制作用。曲霉菌丝激活 NK 细胞、休眠和发芽，而分生孢子和缺乏疏水表面层的 Delta rodA 突变体的分生孢子则不会。我们的结果表明，过继转移的人类 NK 细胞可能是移植环境中潜在的抗真菌工具。
Because natural killer (NK) cells kill tumor cells and combat infections, there is growing interest in adoptively transferring NK cells to hematopoietic stem cell recipients. Unfortunately, in humans, the activity of NK cells against Aspergillus species, the major cause of invasive fungal infection in stem cell recipients, are poorly characterized. Our results show that unstimulated and interleukin-2 prestimulated human NK cells kill Aspergillus fumigatus hyphae but do not affect resting conidia. Killing is also induced by the supernatant of prestimulated NK cells and human perforin. The high levels of interferon-gamma and granulocyte macrophage colony-stimulating factor produced by prestimulated NK cells are significantly reduced by Aspergillus, indicating an immunosuppressive effect of the fungus. Whereas Aspergillus hyphae activate NK cells, resting, and germinating, conidia and conidia of Delta rodA mutants lacking the hydrophobic surface layer do not. Our results suggest that adoptively transferred human NK cells may be a potential antifungal tool in the transplantation context.