Letter | Published:

Surface hydrophobin prevents immune recognition of airborne fungal spores

Nature volume 460, pages 11171121 (27 August 2009) | Download Citation

  • A Corrigendum to this article was published on 17 June 2010

Abstract

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 Aspergillus1,2,3,4. 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 (ΔrodA 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.

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Acknowledgements

We thank J. Vani, Y. Repesse and C. Galeotti for help with dendritic cell experiments; and R. Winkler, S. Behnken and M. Pötsch for help with the MALDI-TOF/TOF analysis. The research of O.K. and A.A.B. was supported by the Deutsche Forschungsgemeinschaft (DFG) Priority Programme 1160, and the EU-STREP Fungwall LSHB-CT-2004-511952 and MANASP LSGBH37899 were also awarded to J.-P.L., A.A.B. and L.R. J.B and S.V.K are supported by INSERM, CNRS and Universities Paris 5 and 6.

Author Contributions J.-P.L. initiated the study; V.A., J.B., L.R. and J.-P.L. designed the research; V.A., C.C., S.P. and J.-P.L. prepared and characterized conidia and fungal materials; J.B., S.R.E. and S.V.K. performed experiments with human dendritic cells; S.B., K.P. and L.R. performed experiments with T-cell clones, murine dendritic cells and macrophages; O.K. and A.A.B. performed protein sequence analysis; V.A., J.B., S.B., O.K., K.P., L.R. and J.-P.L. analysed the results; and V.A., J.B., O.K., L.R. and J.-P.L. wrote the paper.

Author information

Author notes

    • Vishukumar Aimanianda
    •  & Jagadeesh Bayry

    These authors contributed equally to this work.

Affiliations

  1. Unité des Aspergillus, Institut Pasteur, Paris F-75015, France

    • Vishukumar Aimanianda
    • , Cécile Clavaud
    • , Sophie Paris
    •  & Jean-Paul Latgé
  2. INSERM, U 872,

    • Jagadeesh Bayry
    • , Sri Ramulu Elluru
    •  & Srini V. Kaveri
  3. Centre de Recherche des Cordeliers, Université Pierre et Marie Curie–Paris 6, UMR S 872,

    • Jagadeesh Bayry
    • , Sri Ramulu Elluru
    •  & Srini V. Kaveri
  4. Université Paris Descartes, UMR S 872, Paris F-75006, France

    • Jagadeesh Bayry
    • , Sri Ramulu Elluru
    •  & Srini V. Kaveri
  5. Department of Experimental Medicine and Biochemical Sciences,

    • Silvia Bozza
    •  & Luigina Romani
  6. Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia 06122, Italy

    • Katia Perruccio
  7. Department of Molecular and Applied Microbiology, Leibniz-Institute for Natural Product Research and Infection Biology (HKI) and Friedrich Schiller University, 07745 Jena, Germany

    • Olaf Kniemeyer
    •  & Axel A. Brakhage

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Corresponding author

Correspondence to Jean-Paul Latgé.

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DOI

https://doi.org/10.1038/nature08264

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