title: Human dendritic cell subsets display distinct interactions with the pathogenic mould Aspergillus fumigatus.
abstract: The mould Aspergillus fumigatus is primarily an opportunistic pathogen of immunocompromised patients. Once fungal spores have been inhaled they encounter cells of the innate immune system, which include dendritic cells (DCs). DCs are the key antigen-presenting cells of the immune system and distinct subtypes, which differ in terms of origin, morphology and function. This study has systematically compared the interactions between A. fumigatus and myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and monocyte-derived DCs (moDCs). Analyses were performed by time-lapse video microscopy, scanning electron microscopy, plating assays, flow cytometry, 25-plex ELISA and transwell assays. The three subsets of DCs displayed distinct responses to the fungus with mDCs and moDCs showing the greatest similarities. mDCs and moDCs both produced rough convolutions and occasionally phagocytic cups upon exposure to A. fumigatus whereas pDCs maintained a smooth appearance. Both mDCs and moDCs phagocytosed conidia and germ tubes, while pDCs did not phagocytose any fungi. Analysis of cytokine release and maturation markers revealed specific differences in pro- and anti-inflammatory patterns between the different DC subsets. These distinct characteristics between the DC subsets highlight their differences and suggest specific roles of moDCs, mDCs and pDCs during their interaction with A. fumigatus in vivo.
authors.affiliation: Laboratory WÜ4i, Medical Clinic and Policlinic II, University Clinic Würzburg, Würzburg, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Lother
authors.affiliation: Laboratory WÜ4i, Medical Clinic and Policlinic II, University Clinic Würzburg, Würzburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Breitschopf
authors.affiliation: Microbiology Institute - Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Krappmann
authors.affiliation: University of Western Sydney, School of Science and Health, Sydney, NSW, Australia.
authors.forename: C Oliver
authors.initials: CO
authors.lastname: Morton
authors.affiliation: Laboratory WÜ4i, Medical Clinic and Policlinic II, University Clinic Würzburg, Würzburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Bouzani
authors.affiliation: Septomics Research Center, Friedrich-Schiller-University and Leibniz-Institute for Natural Products Research and Infection Biology - Hans-Knöll-Institute, Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.affiliation: Institute of Experimental Immunology and Imaging, University Duisburg-Essen, Essen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gunzer
authors.affiliation: Institute of Experimental Immunology and Imaging, University Duisburg-Essen, Essen, Germany.
authors.forename: Mike
authors.initials: M
authors.lastname: Hasenberg
authors.affiliation: Laboratory WÜ4i, Medical Clinic and Policlinic II, University Clinic Würzburg, Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Laboratory WÜ4i, Medical Clinic and Policlinic II, University Clinic Würzburg, Würzburg, Germany. Electronic address: loeffler_j@ukw.de.
authors.forename: Juergen
authors.initials: J
authors.lastname: Loeffler
mesh_terms: D001232:Aspergillus fumigatus / Q000276:immunology*; D054443:Cell Migration Assays; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D006801:Humans; D008855:Microscopy, Electron, Scanning; D018715:Microscopy, Video; D010587:Phagocytosis; D059008:Time-Lapse Imaging
keywords: Aspergillus fumigatus; Dendritic cells; Human; Monocyte derived dendritic cells (moDCs); Myeloid dendritic cells (mDCs); Plasmacytoid dendritic cells (pDCs)