Surface hydrophobin prevents immune recognition of airborne fungal spores

• Published in: Nature (London) Vol. 460; no. 7259; pp. 1117 - 1121
• Main Authors: Aimanianda, Vishukumar, Bayry, Jagadeesh, Bozza, Silvia, Kniemeyer, Olaf, Perruccio, Katia, Elluru, Sri Ramulu, Clavaud, Cécile, Paris, Sophie, Brakhage, Axel A., Kaveri, Srini V., Romani, Luigina, Latgé, Jean-Paul
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.08.2009; Nature Publishing Group
• Subjects: Adoptive Transfer; Air Microbiology; Allergens; Alternaria; Animals; Antigens, Fungal; Antigens, Fungal - chemistry; Antigens, Fungal - genetics; Antigens, Fungal - immunology; Antigens, Plant; Aspergillus fumigatus; Aspergillus fumigatus - chemistry; Aspergillus fumigatus - immunology; Aspergillus fumigatus - physiology; Biological and medical sciences; Cathepsins; CD4-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes - immunology; Cells; Cells, Cultured; Cladosporium; Dendritic Cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - transplantation; Fundamental and applied biological sciences. Psychology; Fungal Proteins; Fungi; Growth, nutrition, metabolism, transports, enzymes. Molecular biology; Humanities and Social Sciences; Humans; Hydrofluoric Acid; Hydrofluoric Acid - chemistry; Immune response; Immune System; Immune System - immunology; Immunology; Inhalation; Innate immunity; letter; Life Sciences; Lymphocyte Activation; Macrophages, Alveolar; Macrophages, Alveolar - immunology; Mice; Mice, Inbred C57BL; Microbiology; Microbiology and Parasitology; multidisciplinary; Mycology; Penicillium; Physiological aspects; Proteins; Science; Science (multidisciplinary); Spores, Fungal; Spores, Fungal - chemistry; Spores, Fungal - genetics; Spores, Fungal - immunology; T cells; Fungi; Dendritic cell; In vivo; Animal microorganism relation; Pulmonary alveolus; Hydrophobic compound; Host agent relation; Respiratory system; In vitro; Cell surface; Spores; Macrophage
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature08264

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 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 (Δ 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.