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Infect. Immun. doi:10.1128/IAI.01037-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The opportunistic human pathogenic fungus Aspergillus fumigatus evades the host complement system

Department of Molecular and Applied Microbiology; Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (HKI) Jena, Germany; Friedrich Schiller University, Jena, Germany

^* To whom correspondence should be addressed. Email: Axel.Brakhage{at}hki-jena.de.

	Abstract

The opportunistic human pathogenic fungus Aspergillus fumigatus causes severe systemic infections and is a major cause of fungal infections in immunocompromized 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 binding of host complement regulators. Binding of factor H and factor H like protein 1 (FHL-1) from human serum to A. fumigatus conidia was shown by adsorption assays and immunostaining. In addition, factor H related protein 1 (FHR-1) did also bind to conidia. Adsorption assays with recombinant factor H mutants were used to localize the binding domains. One binding region was identified within the N-terminal short consensus repeats (SCRs) 1-7 and a second one within the 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 factor H, FHR-1, FHL-1 and plasminogen, thus indicating developmentally regulated expression of A. fumigatus surface ligands. Both factor H and plasminogen maintained regulating activity when bound to the conidial surface. Bound factor H acted as cofactor to factor I-mediated cleavage of C3b. Plasminogen showed proteolytic activity when activated to the plasmin by uPA. These data show that A. fumigatus conidia bind complement regulators and the bound host regulators may contribute evasion of host complement attack.