title: Influence of Platelet-rich Plasma on the immune response of human monocyte-derived dendritic cells and macrophages stimulated with Aspergillus fumigatus.
abstract: Dendritic cells (DCs) and macrophages (MΦ) are critical for protection against pathogenic fungi including Aspergillus fumigatus. To analyze the role of platelets in the innate immune response, human DCs and MΦs were challenged with A. fumigatus in presence or absence of human platelet rich plasma (PRP). Gene expression analyses and functional investigations were performed. A systems biological approach was used for initial modelling of the DC - A. fumigatus interaction. DCs in a quiescent state together with different corresponding activation states were validated using gene expression data from DCs and MΦ stimulated with A. fumigatus. To characterize the influence of platelets on the immune response of DCs and MΦ to A. fumigatus, we experimentally quantified their cytokine secretion, phagocytic capacity, maturation, and metabolic activity with or without platelets. PRP in combination with A. fumigatus treatment resulted in the highest expression of the maturation markers CD80, CD83 and CD86 in DCs. Furthermore, PRP enhanced the capacity of macrophages and DCs to phagocytose A. fumigatus conidia. In parallel, PRP in combination with the innate immune cells significantly reduced the metabolic activity of the fungus. Interestingly, A. fumigatus and PRP stimulated MΦ showed a significantly reduced gene expression and secretion of IL6 while PRP only reduced the IL-6 secretion of A. fumigatus stimulated DCs. The in silico systems biological model correlated well with these experimental data. Different modules centrally involved in DC function became clearly apparent, including DC maturation, cytokine response and apoptosis pathways. Taken together, the ability of PRP to suppress IL-6 release of human DCs might prevent local excessive inflammatory hemorrhage, tissue infarction and necrosis in the human lung.
authors.affiliation: Department of Internal Medicine, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Czakai
authors.affiliation: Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dittrich
authors.affiliation: Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kaltdorf
authors.affiliation: Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Müller
authors.affiliation: Microbiology Institute-Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Krappmann
authors.affiliation: Department of Internal Medicine, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Anette
authors.initials: A
authors.lastname: Schedler
authors.affiliation: IMGM Laboratories GmbH, Planegg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.affiliation: Deparment of Bioinformatics, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Sybille
authors.initials: S
authors.lastname: Dühring
authors.affiliation: Deparment of Bioinformatics, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schuster
authors.affiliation: Hygiene und Medizinische Mikrobiologie, Medizinische Universität Innsbruck, Innsbruck, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Speth
authors.affiliation: Hygiene und Medizinische Mikrobiologie, Medizinische Universität Innsbruck, Innsbruck, Austria.
authors.forename: Günter
authors.initials: G
authors.lastname: Rambach
authors.affiliation: Department of Internal Medicine, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dandekar
authors.affiliation: Department of Internal Medicine, University Hospital of Würzburg, Würzburg, Germany. Electronic address: loeffler_j@ukw.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Löffler
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D001232:Aspergillus fumigatus / Q000276:immunology*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D020869:Gene Expression Profiling; D064368:Healthy Volunteers; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D010587:Phagocytosis; D053657:Platelet-Rich Plasma / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D016207:Cytokines
keywords: Boolean model; Gene ontology; IL-6; Network; Platelets; Transcriptional profiling