Department of Internal Medicine II, University Hospital Wuerzburg, Wuerzburg, Germany.
Department of Biotechnology & Biophysics Biocenter, University of Wuerzburg, Wuerzburg, Germany.
PLoS Pathog. 2024 Jun 18;20(6):e1012315. doi: 10.1371/journal.ppat.1012315. eCollection 2024 Jun.
Invasive aspergillosis causes significant morbidity and mortality in immunocompromised patients. Natural killer (NK) cells are pivotal for antifungal defense. Thus far, CD56 is the only known pathogen recognition receptor on NK cells triggering potent antifungal activity against Aspergillus fumigatus. However, the underlying cellular mechanisms and the fungal ligand of CD56 have remained unknown. Using purified cell wall components, biochemical treatments, and ger mutants with altered cell wall composition, we herein found that CD56 interacts with the A. fumigatus cell wall carbohydrate galactosaminogalactan (GAG). This interaction induced NK-cell activation, degranulation, and secretion of immune-enhancing chemokines and cytotoxic effectors. Supernatants from GAG-stimulated NK cells elicited antifungal activity and enhanced antifungal effector responses of polymorphonuclear cells. In conclusion, we identified A. fumigatus GAG as a ligand of CD56 on human primary NK cells, stimulating potent antifungal effector responses and activating other immune cells.
侵袭性曲霉菌病会导致免疫功能低下患者出现严重的发病率和死亡率。自然杀伤 (NK) 细胞是抗真菌防御的关键。到目前为止，CD56 是 NK 细胞上唯一已知的病原体识别受体，它能触发针对烟曲霉的强大抗真菌活性。然而，其潜在的细胞机制和 CD56 的真菌配体仍不清楚。使用纯化的细胞壁成分、生化处理和细胞壁成分改变的 ger 突变体，我们在此发现 CD56 与烟曲霉细胞壁碳水化合物半乳氨基半乳糖 (GAG) 相互作用。这种相互作用诱导 NK 细胞活化、脱颗粒以及免疫增强趋化因子和细胞毒性效应物的分泌。来自 GAG 刺激的 NK 细胞的上清液可引发抗真菌活性，并增强多形核细胞的抗真菌效应器反应。总之，我们鉴定出烟曲霉 GAG 是人类原代 NK 细胞上 CD56 的配体，可刺激强大的抗真菌效应器反应并激活其他免疫细胞。
