The Opportunistic Human Pathogenic FungusAspergillus fumigatusEvades the Host Complement System
Open Access
- 1 February 2008
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 76 (2), 820-827
- https://doi.org/10.1128/iai.01037-07
Abstract
The opportunistic human pathogenic fungusAspergillus fumigatuscauses severe systemic infections and is a major cause of fungal infections in immunocompromised patients.A. fumigatusconidia activate the alternative pathway of the complement system. In order to assess the mechanisms by whichA. fumigatusevades the activated complement system, we analyzed the binding of host complement regulators toA. fumigatus. The binding of factor H and factor H-like protein 1 (FHL-1) from human sera toA. fumigatusconidia 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 toA. fumigatusconidia. In contrast to conidia, other developmental stages ofA. fumigatus, like swollen conidia or hyphae, did not bind to factor H, FHR-1, FHL-1, and plasminogen, thus indicating the developmentally regulated expression ofA. fumigatussurface 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 thatA. fumigatusconidia bind to complement regulators, and these bound host regulators may contribute to evasion of a host complement attack.Keywords
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