Surface hydrophobin prevents immune recognition of airborne fungal spores
Surface hydrophobin prevents immune recognition of airborne fungal spores
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DOI：
10.1038/nature08264
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发表时间：
2009-08-27
期刊：
影响因子：
64.8
通讯作者：
Latge, Jean-Paul
中科院分区：
文献类型：
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作者：
Aimanianda, Vishukumar;Bayry, Jagadeesh;Latge, Jean-Paul
我们呼吸的空气中每立方米充满了数千个真菌孢子(分生孢子)，在某些堆肥环境中，每立方米很容易超过109个。它们起源于100多种真菌，主要属于枝孢属、青霉属、交链孢属和曲霉属(1-4)。虽然这些分生孢子含有许多抗原和过敏原(5-7)，但尚不清楚为什么空气传播的真菌微生物群不能持续激活宿主的固有免疫细胞，也不会在吸入后引发有害的炎症反应。在这里，我们展示了休眠分生孢子的表层掩盖了免疫系统对它们的识别，从而阻止了免疫反应。为了探索这一点，我们使用了空气微生物区系中的几个真菌成员，包括人类机会真菌病原体烟曲霉，在体外用树突状细胞和肺泡巨噬细胞进行检测，并在体内进行小鼠实验。在烟曲霉菌中，这个表面的“小杆层”是由疏水性的RodA蛋白通过糖基磷脂酰肌醇残基共价结合到分生孢子细胞壁上。从烟曲霉分生孢子中提取的RODA具有免疫惰性，不能诱导树突状细胞或肺泡巨噬细胞的成熟和激活，在体内也不能激活辅助性T细胞免疫应答。通过化学方法(使用氢氟酸)、遗传方法(Delta Roda突变体)或生物方法(萌发)去除这种表面的“小棒/疏水层”，可导致分生孢子形态诱导免疫激活。所有这些观察表明，孢子细胞表面的疏水小棒层对空气中的霉菌具有免疫沉默作用。
The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 10 9 per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus(1-4). Although these conidia contain many antigens and allergens(5-7), it is not known why airborne fungal microflora do not activate the host innate immune cells continuously and do not induce detrimental inflammatory responses following their inhalation. Here we show that the surface layer on the dormant conidia masks their recognition by the immune system and hence prevents immune response. To explore this, we used several fungal members of the airborne microflora, including the human opportunistic fungal pathogen Aspergillus fumigatus, in in vitro assays with dendritic cells and alveolar macrophages and in in vivo murine experiments. In A. fumigatus, this surface 'rodlet layer' is composed of hydrophobic RodA protein covalently bound to the conidial cell wall through glycosylphosphatidylinositol-remnants. RodA extracted from conidia of A. fumigatus was immunologically inert and did not induce dendritic cell or alveolar macrophage maturation and activation, and failed to activate helper T-cell immune responses in vivo. The removal of this surface 'rodlet/hydrophobin layer' either chemically (using hydrofluoric acid), genetically (Delta rodA mutant) or biologically (germination) resulted in conidial morphotypes inducing immune activation. All these observations show that the hydrophobic rodlet layer on the conidial cell surface immunologically silences airborne moulds.