title: Role of ficolin-A and lectin complement pathway in the innate defense against pathogenic Aspergillus species.
abstract: Aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. Innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. We have shown that the complement component ficolin-A significantly binds to Aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by N-acetylglucosamine and N-acetylgalactosamine. Calcium-independent binding to Aspergillus fumigatus and A. terreus was observed, but binding to A. flavus and A. niger was calcium dependent. Ficolin-A binding to conidia was increased under low-pH conditions, and opsonization led to enhanced binding of conidia to A549 airway epithelial cells. In investigations of the lectin pathway of complement activation, ficolin-A-opsonized conidia did not lead to lectin pathway-specific C4 deposition. In contrast, the collectin mannose binding lectin C (MBL-C) but not MBL-A led to efficient lectin pathway activation on A. fumigatus in the absence of ficolin-A. In addition, ficolin-A opsonization led to a modulation of the proinflammatory cytokine interleukin-8. We conclude that ficolin-A may play an important role in the innate defense against Aspergillus by opsonizing conidia, immobilizing this fungus through enhanced adherence to epithelial cells and modulation of inflammation. However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A.
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bidula
authors.forename: Hany
authors.initials: H
authors.lastname: Kenawy
authors.forename: Youssif M
authors.initials: YM
authors.lastname: Ali
authors.forename: Darren
authors.initials: D
authors.lastname: Sexton
authors.forename: Wilhelm J
authors.initials: WJ
authors.lastname: Schwaeble
authors.forename: Silke
authors.initials: S
authors.lastname: Schelenz
mesh_terms: D000818:Animals; D001230:Aspergillus / Q000276:immunology*; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism; D037102:Lectins / Q000502:physiology*; D051381:Rats; D000097604:Ficolins
chemical_list: D016209:Interleukin-8; D037102:Lectins; D000097604:Ficolins