Surface hydrophobin prevents immune recognition of airborne fungal spores

Breathe easy: why inhaled fungal spores don't provoke an immune reaction Every day we inhale thousands of tiny fungal spores (conidia), originating from many different fungal species. Yet although these spores are packed with antigens and allergens, their inhalation does not continuously activate our innate immune cells or provoke inflammatory responses. A series of immunological, biochemical and genetic experiments shows why: immune recognition of these spores is prevented by a hydrophobic layer of rodlet proteins covering the conidial surface. If this layer is removed, spores activate the immune system. A pathogenic spore equipped with this defensive layer might lie dormant beyond host defences until conditions are suitable for germination. Therapeutically the robust nature of the rodlet proteins might be exploited to generate nanoparticles containing embedded molecules targeted to a specific location in the body, or optimized for sustained delivery. Fungal spores are ubiquitous in the air we breathe and contain many antigens and allergens, and yet they neither continuously activate the host innate immune cells nor induce detrimental inflammatory responses after their inhalation. Here, the surface layer on dormant spores is shown to mask their recognition by the immune system and hence prevent an immune response. 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 , 2 , 3 , 4 . Although these conidia contain many antigens and allergens 5 , 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 extracte