Inflammasomes are important sentinels of innate immune defence that are activated in response to diverse stimuli, including pathogen-associated molecular patterns (PAMPs) 1 . Activation of the inflammasome provides host defence against aspergillosis 2 , 3 , which is a major health concern for patients who are immunocompromised. However, the Aspergillus fumigatus PAMPs that are responsible for inflammasome activation are not known. Here we show that the polysaccharide galactosaminogalactan (GAG) of A. fumigatus is a PAMP that activates the NLRP3 inflammasome. The binding of GAG to ribosomal proteins inhibited cellular translation machinery, and thus activated the NLRP3 inflammasome. The galactosamine moiety bound to ribosomal proteins and blocked cellular translation, which triggered activation of the NLRP3 inflammasome. In mice, a GAG-deficient Aspergillus mutant (Δ gt4c ) did not elicit protective activation of the inflammasome, and this strain exhibited enhanced virulence. Moreover, administration of GAG protected mice from colitis induced by dextran sulfate sodium in an inflammasome-dependent manner. Thus, ribosomes connect the sensing of this fungal PAMP to the activation of an innate immune response. Galactosaminogalactan of Aspergillus fumigatus acts as a pathogen-associated molecular pattern that activates the NLRP3 inflammasome, which is crucial for anti-fungal host defence.

中文翻译：

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半乳糖胺半乳聚糖激活炎症小体以提供宿主保护

炎症小体是先天免疫防御的重要哨兵，可响应多种刺激而激活，包括病原体相关分子模式 (PAMP) 1 。炎症小体的激活提供宿主防御曲霉病 2 、 3 ，这是免疫功能低下患者的主要健康问题。然而，负责炎症小体激活的烟曲霉 PAMP 尚不清楚。在这里，我们表明烟曲霉的多糖半乳糖氨基半乳聚糖 (GAG) 是一种激活 NLRP3 炎性体的 PAMP。GAG 与核糖体蛋白的结合抑制了细胞翻译机制，从而激活了 NLRP3 炎症小体。半乳糖胺部分与核糖体蛋白结合并阻止细胞翻译，从而触发 NLRP3 炎症小体的激活。在小鼠中，GAG 缺陷曲霉突变体 (Δ gt4c ) 不会引起炎症小体的保护性激活，并且该菌株表现出增强的毒力。此外，GAG 的给药以炎性体依赖性方式保护小鼠免受由葡聚糖硫酸钠诱导的结肠炎。因此，核糖体将这种真菌 PAMP 的感知与先天免疫反应的激活联系起来。烟曲霉的半乳糖胺半乳聚糖作为病原体相关的分子模式，激活 NLRP3 炎症小体，这对于抗真菌宿主防御至关重要。核糖体将这种真菌 PAMP 的感知与先天免疫反应的激活联系起来。烟曲霉的半乳糖胺半乳聚糖作为病原体相关的分子模式，激活 NLRP3 炎症小体，这对于抗真菌宿主防御至关重要。核糖体将这种真菌 PAMP 的感知与先天免疫反应的激活联系起来。烟曲霉的半乳糖胺半乳聚糖作为病原体相关的分子模式，激活 NLRP3 炎症小体，这对于抗真菌宿主防御至关重要。