Lehrnbecher Thomas, Schmidt Stanislaw
Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany.
Med Mycol. 2019 Apr 1;57(Supplement_2):S206-S210. doi: 10.1093/mmy/myy034.
There is growing evidence that natural killer (NK) cells play an important role in the host response to Aspergillus spp. In vitro data clearly demonstrate that both murine and human NK cells are able to damage Aspergillus. NK cells exert direct antifungal activity via cytotoxic molecules such as perforin, and NK cell-derived cytokines and interferons modulate proliferation and activation of a variety of immune cells in order to fight the fungus. However, in turn, Aspergillus is able to exhibit immunosuppressive effects on NK cells. Antibody-mediated depletion of NK cells in neutropenic mice infected with A. fumigatus further impairs clearance of the pathogen from the lungs and results in a higher mortality as compared to animals with NK cells. Clinical data on the impact of NK cells in the antifungal host response are less clear, as different arms of the human immune system are involved, which interact and overlap in a complex network. Future studies must better characterize the interaction of NK cells and Aspergillus and to clarify the benefit and potential risks of using NK cells as adoptive immunotherapy in patients suffering from invasive aspergillosis, which may be a significant step toward decreasing morbidity and mortality of these patients.
越来越多的证据表明，自然杀伤（NK）细胞在宿主对曲霉属真菌的反应中发挥重要作用。体外数据清楚地表明，小鼠和人类NK细胞都能够损伤曲霉。NK细胞通过穿孔素等细胞毒性分子发挥直接抗真菌活性，并且NK细胞衍生的细胞因子和干扰素调节多种免疫细胞的增殖和活化，以对抗真菌。然而，反过来，曲霉能够对NK细胞表现出免疫抑制作用。在感染烟曲霉的中性粒细胞减少小鼠中，抗体介导的NK细胞耗竭进一步损害了肺部病原体的清除，与具有NK细胞的动物相比，导致更高的死亡率。关于NK细胞在抗真菌宿主反应中影响的临床数据尚不明确，因为人类免疫系统的不同部分都参与其中，它们在一个复杂的网络中相互作用和重叠。未来的研究必须更好地表征NK细胞与曲霉之间的相互作用，并阐明在侵袭性曲霉病患者中使用NK细胞作为过继性免疫疗法的益处和潜在风险，这可能是朝着降低这些患者的发病率和死亡率迈出的重要一步。
