title: CD11c.DTR mice develop a fatal fulminant myocarditis after local or systemic treatment with diphtheria toxin.
abstract: To assess the role of alveolar macrophages (AMs) during a pulmonary Aspergillus fumigatus infection AMs were depleted by intratracheal application of diphtheria toxin (DTX) to transgenic CD11c.DTR mice prior to fungal infection. Unexpectedly, all CD11c.DTR mice treated with DTX died within 4-5 days, whether being infected with A. fumigatus or not. Despite measurable impact of DTX on lung functional parameters, these constrictions could not explain the high mortality rate. Instead, DTX-treated CD11c.DTR animals developed fulminant myocarditis (FM) characterized by massive leukocyte infiltration and myocardial cell destruction, including central parts of the heart's stimulus transmission system. In fact, standard limb lead ECG recordings of diseased but not healthy mice showed a "Brugada"-like pattern with an abnormally high ST segment pointing to enhanced susceptibility for potential lethal arrhythmias. While CD11c.DTR mice are extensively used for the characterization of CD11c(+) cells, including dendritic cells, several studies have already mentioned adverse side effects following DTX treatment. Our results demonstrate that this limitation is based on severe myocarditis but not on the expected lung constrictions, and has to be taken into consideration if this animal model is used. Based on these properties, however, the CD11c.DTR mouse might serve as useful animal model for FM.
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Männ
authors.affiliation: Department of Research, Experimental Critical Care Medicine, University Hospital, Basel, Switzerland.
authors.forename: Nora
authors.initials: N
authors.lastname: Kochupurakkal
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Aachen, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Martin
authors.affiliation: Institute of Pediatrics, University Hospital Aachen, Aachen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Verjans
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Klingberg
authors.affiliation: Department of Otorhinolaryngology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Sody
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kraus
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Jill
authors.initials: J
authors.lastname: Dalimot
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Eileen
authors.initials: E
authors.lastname: Bergmüller
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.affiliation: Imaging Center Essen, Electron Microscopy Unit, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Voortman
authors.affiliation: Imaging Center Essen, Electron Microscopy Unit, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Winterhager
authors.affiliation: Department of Otorhinolaryngology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
authors.affiliation: Institute of Experimental Immunology, Rheinische Friedrich Wilhelms University, Bonn, Germany.
authors.forename: Natalio
authors.initials: N
authors.lastname: Garbi
authors.affiliation: Gemeinschaftspraxis für Pathologie, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Kurrer
authors.affiliation: Division of Cardioimmunology, Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland.|Department of Medicine, GZO-Zurich Regional Health Center, Wetzikon, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Eriksson
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gunzer
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Mike
authors.initials: M
authors.lastname: Hasenberg
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus; D039521:CD11c Antigen / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology*; D004167:Diphtheria Toxin / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004562:Electrocardiography; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009205:Myocarditis / Q000139:chemically induced*; D009206:Myocardium / Q000473:pathology*
chemical_list: D039521:CD11c Antigen; D004167:Diphtheria Toxin
keywords: CD11c.DTR ⋅ Conditional knockout ⋅ Diphtheria toxin ⋅ Infection ⋅ Myocarditis ⋅ Transgenic mice