title: Factor H Binds to Extracellular DNA Traps Released from Human Blood Monocytes in Response toCandida albicans.
abstract: Upon systemic infection with human pathogenic yeastCandida albicans(C. albicans), human monocytes and polymorph nuclear neutrophilic granulocytes are the first immune cells to respond and come into contact withC. albicans. Monocytes exert immediate candidacidal activity and inhibit germination, mediate phagocytosis, and kill fungal cells. Here, we show that human monocytes spontaneously respond toC. albicanscellsviaphagocytosis, decondensation of nuclear DNA, and release of this decondensed DNA in the form of extracellular traps (called monocytic extracellular traps: MoETs). Both subtypes of monocytes (CD14++CD16-/CD14+CD16+) formed MoETs within the first hours upon contact withC. albicans. MoETs were characterized by the presence of citrullinated histone, myeloperoxidase, lactoferrin, and elastase. MoETs were also formed in response toStaphylococcus aureusandEscherichia coli, indicating a general reaction of monocytes to infectious microbes. MoET induction differs from extracellular trap formation in macrophages as MoETs are not triggered by simvastatin, an inhibitor of cholesterol synthesis and inducer of extracellular traps in macrophages. Extracellular traps from both monocytes and neutrophils activate complement and C3b is deposited. However, factor H (FH) bindsviaC3b to the extracellular DNA, mediates cofactor activity, and inhibits the induction of the inflammatory cytokine interleukin-1 beta in monocytes. Altogether, the results show that human monocytes release extracellular DNA traps in response toC. albicansand that these traps finally bind FHviaC3b to presumably support clearance without further inflammation.
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology , Jena , Germany.
authors.forename: Luke D
authors.initials: LD
authors.lastname: Halder
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology , Jena , Germany.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Abdelfatah
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology , Jena , Germany.
authors.forename: Emeraldo A H
authors.initials: EA
authors.lastname: Jo
authors.affiliation: Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany; Friedrich-Schiller University, Jena, Germany.
authors.forename: Ilse D
authors.initials: ID
authors.lastname: Jacobsen
authors.affiliation: Center for Electron Microscopy of the University Hospital Jena , Jena , Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Westermann
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg , Würzburg , Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Beyersdorf
authors.affiliation: Institute of Nutrition, Friedrich-Schiller University , Jena , Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lorkowski
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany; Friedrich-Schiller University, Jena, Germany.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology , Jena , Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Skerka
keywords: Candida; DNA traps; MPO; factor H; monocytes