title: Hypoxia attenuates anti-Aspergillus fumigatus immune responses initiated by human dendritic cells.
abstract: Aspergillus fumigatus is an opportunistic mould that causes invasive pulmonary aspergillosis (IPA), a life-threatening infection in immunocompromised patients. During the course of IPA, localised areas of tissue hypoxia occur. Bacterial infection models revealed that hypoxic microenvironments modulate the function of host immune cells. However, the influence of hypoxia on anti-fungal immunity has been largely unknown. We evaluated the impact of hypoxia on the human anti-A. fumigatus immune response. Human monocyte-derived dendritic cells (DCs) were stimulated in vitro with germ tubes of A. fumigatus under normoxia or hypoxia (1% O2 ), followed by analysis of DC viability, maturation and cytokine release. While DC viability was unaffected, hypoxia attenuated cytokine release from DCs and maturation of DCs upon stimulation with A. fumigatus. These data suggest that hypoxia at the site of A. fumigatus infection inhibits full activation and function of human DCs. Thereby, this study identified hypoxia as a crucial immune-modulating factor in the human anti-fungal immune response that might influence the course and outcome of IPA in immunocompromised patients.
authors.affiliation: Medical Clinic and Polyclinic II, University Hospital, Wuerzburg, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Fliesser
authors.affiliation: Medical Clinic and Polyclinic II, University Hospital, Wuerzburg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Wallstein
authors.affiliation: Septomics Research Centre, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute, Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.affiliation: Medical Clinic and Polyclinic II, University Hospital, Wuerzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Medical Clinic and Polyclinic II, University Hospital, Wuerzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Löffler
mesh_terms: D001232:Aspergillus fumigatus / Q000276:immunology*; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016867:Immunocompromised Host; D056747:Immunomodulation; D055744:Invasive Pulmonary Aspergillosis / Q000276:immunology*
chemical_list: D016207:Cytokines
keywords: Aspergillus fumigatus; dendritic cells; hypoxia; immune response; invasive pulmonary aspergillosis