title: Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens.
abstract: Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils, and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4(+) or CD8(+) T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b(+) myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b(+) myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions.
authors.affiliation: Department of Medicine II, Würzburg University HospitalWürzburg, Germany; Research Center for Infectious Diseases, Julius-Maximilians-University WürzburgWürzburg, Germany; Interdisciplinary Center for Clinical Science Research LaboratoryWuürzburg, Germany; Graduate School of Life Sciences WürzburgWürzburg, Germany.
authors.forename: Natarajaswamy
authors.initials: N
authors.lastname: Kalleda
authors.affiliation: Department of Medicine II, Würzburg University HospitalWürzburg, Germany; Research Center for Infectious Diseases, Julius-Maximilians-University WürzburgWürzburg, Germany.
authors.forename: Jorge
authors.initials: J
authors.lastname: Amich
authors.affiliation: Department of Medicine II, Würzburg University Hospital Würzburg, Germany.
authors.forename: Berkan
authors.initials: B
authors.lastname: Arslan
authors.affiliation: Max Planck Institute for Chemical Ecology Jena, Germany.
authors.forename: Spoorthi
authors.initials: S
authors.lastname: Poreddy
authors.affiliation: Department of Medicine II, Würzburg University Hospital Würzburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Mattenheimer
authors.affiliation: Department of Medicine II, Würzburg University Hospital Würzburg, Germany.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Mokhtari
authors.affiliation: Department of Medicine II, Würzburg University Hospital Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Friedrich Schiller University JenaJena, Germany; Institute for Microbiology, Friedrich Schiller University JenaJena, Germany; Fungal Genetics and Biology Group, University of Nottingham, School of Life SciencesNottingham, UK.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brock
authors.affiliation: Rudolf Virchow Center, Julius-Maximilians-University Würzburg Würzburg, Germany.
authors.forename: Katrin Gertrud
authors.initials: KG
authors.lastname: Heinze
authors.affiliation: Department of Medicine II, Würzburg University HospitalWürzburg, Germany; Research Center for Infectious Diseases, Julius-Maximilians-University WürzburgWürzburg, Germany; Interdisciplinary Center for Clinical Science Research LaboratoryWuürzburg, Germany; Graduate School of Life Sciences WürzburgWürzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beilhack
keywords: Aspergillus fumigatus; CD11b+ myeloid cells; corticosteroids and cyclophosphamide; immune cell recruitment