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Infection and Immunity, February 2008, p. 820-827, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01037-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Opportunistic Human Pathogenic Fungus Aspergillus fumigatus Evades the Host Complement System{triangledown}

Judith Behnsen,1 Andrea Hartmann,2 Jeannette Schmaler,1 Alexander Gehrke,1 Axel A. Brakhage,1,3* and Peter F. Zipfel2,3

Department of Molecular and Applied Microbiology,1 Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knöll Institute, Jena, Germany,2 Friedrich Schiller University, Jena, Germany3

Received 27 July 2007/ Returned for modification 16 September 2007/ Accepted 11 November 2007

The opportunistic human pathogenic fungus Aspergillus fumigatus causes severe systemic infections and is a major cause of fungal infections in immunocompromised patients. A. fumigatus conidia activate the alternative pathway of the complement system. In order to assess the mechanisms by which A. fumigatus evades the activated complement system, we analyzed the binding of host complement regulators to A. fumigatus. The binding of factor H and factor H-like protein 1 (FHL-1) from human sera to A. fumigatus conidia was shown by adsorption assays and immunostaining. In addition, factor H-related protein 1 (FHR-1) bound to conidia. Adsorption assays with recombinant factor H mutants were used to localize the binding domains. One binding region was identified within N-terminal short consensus repeats (SCRs) 1 to 7 and a second one within C-terminal SCR 20. Plasminogen was identified as the fourth host regulatory molecule that binds to A. fumigatus conidia. In contrast to conidia, other developmental stages of A. fumigatus, like swollen conidia or hyphae, did not bind to factor H, FHR-1, FHL-1, and plasminogen, thus indicating the developmentally regulated expression of A. fumigatus surface ligands. Both factor H and plasminogen maintained regulating activity when they were bound to the conidial surface. Bound factor H acted as a cofactor to the factor I-mediated cleavage of C3b. Plasminogen showed proteolytic activity when activated to plasmin by urokinase-type plasminogen activator. These data show that A. fumigatus conidia bind to complement regulators, and these bound host regulators may contribute to evasion of a host complement attack.

* Corresponding author. Mailing address: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstrasse 11a, Jena, Germany. Phone: 49 (03641) 65 6601. Fax: 49 (03641) 65 6603. E-mail: Axel.Brakhage{at}hki-jena.de

{triangledown} Published ahead of print on 26 November 2007.

Editor: A. Casadevall

Infection and Immunity, February 2008, p. 820-827, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01037-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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