本期封面所示为烟曲霉分生孢子的一幅扫描电子显微镜照片(由S. Guadagnini、 J. M. Panaud 和A. Beauvais提供),烟曲霉是这项研究中所使用的人类病原体之一。
我们每天都会吸入数以千计的微小真菌孢子(分生孢子),它们来自很多不同的真菌菌种。然而,虽然这些孢子内含抗原和过敏原,但它们的吸入并不会连续激发我们的先天免疫细胞或引起炎症反应。
一系列免疫学、生物医学和遗传学实验说明了原因是什么:这些孢子的免疫识别被覆盖分生孢子表面的小棒蛋白所构成的一个憎水层阻止了。如果将这个憎水层去掉,孢子就会激发免疫系统。具备这一防卫层的一个致病性孢子也许会一直处于休眠状态,躲开宿主防卫系统,直到条件合适时才萌发。从治疗角度来讲,小棒蛋白的这种鲁棒性也许可被利用来生成纳米颗粒,后者含有嵌入的分子,这些分子以身体内某一特定位置为目标,或经过了优化处理,可以持续向体内输送。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 460, 1117-1121 (27 August 2009) | doi:10.1038/nature08264
Surface hydrophobin prevents immune recognition of airborne fungal spores
Vishukumar Aimanianda1,8, Jagadeesh Bayry2,3,4,8, Silvia Bozza5, Olaf Kniemeyer7, Katia Perruccio6, Sri Ramulu Elluru2,3,4, Cécile Clavaud1, Sophie Paris1, Axel A. Brakhage7, Srini V. Kaveri2,3,4, Luigina Romani5 & Jean-Paul Latgé1
1 Unité des Aspergillus, Institut Pasteur, Paris F-75015, France
2 INSERM, U 872,
3 Centre de Recherche des Cordeliers, Université Pierre et Marie Curie–Paris 6, UMR S 872,
4 Université Paris Descartes, UMR S 872, Paris F-75006, France
5 Department of Experimental Medicine and Biochemical Sciences,
6 Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia 06122, Italy
7 Department of Molecular and Applied Microbiology, Leibniz-Institute for Natural Product Research and Infection Biology (HKI) and Friedrich Schiller University, 07745 Jena, Germany
8 These authors contributed equally to this work.
The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 109 per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus 1, 2, 3, 4. Although these conidia contain many antigens and allergens5, 6, 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 (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.