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Opposing roles of resident and infiltrating immune cells in the defense against Legionella longbeachae via IL-18R/IFN-γ/ROS axis in mice.
Oberkircher, Lara M; Scheiding, Victoria M; Rafeld, H Linda; Hanssen, Eric; Hansen, Jan N; Fleischmann, Markus J; Kessler, Nina; Pitsch, David; Wachten, Dagmar; Kastenmüller, Wolfgang; Brown, Andrew S; Hartland, Elizabeth L; van Driel, Ian R; Ng, Garrett Z; Garbi, Natalio.
Afiliación
  • Oberkircher LM; Institute of Molecular Medicine and Experimental Immunology, Faculty of Medicine, University of Bonn, Bonn, Germany; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Australia; Department of Biochemistry and Pharmacology, University of Melbourne, Mel
  • Scheiding VM; Institute of Molecular Medicine and Experimental Immunology, Faculty of Medicine, University of Bonn, Bonn, Germany; Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Australia; Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Au
  • Rafeld HL; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Australia; Life & Medical-Sciences Institute, University of Bonn, Bonn, Germany.
  • Hanssen E; Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Australia; Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia; Ian Holmes Imaging Centre, University of Melbourne, Melbourne, Australia.
  • Hansen JN; Institute of Innate Immunity, Faculty of Medicine, University of Bonn, Bonn, Germany.
  • Fleischmann MJ; Institute of Molecular Medicine and Experimental Immunology, Faculty of Medicine, University of Bonn, Bonn, Germany; Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Australia; Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Au
  • Kessler N; Institute of Molecular Medicine and Experimental Immunology, Faculty of Medicine, University of Bonn, Bonn, Germany.
  • Pitsch D; Institute of Molecular Medicine and Experimental Immunology, Faculty of Medicine, University of Bonn, Bonn, Germany.
  • Wachten D; Institute of Innate Immunity, Faculty of Medicine, University of Bonn, Bonn, Germany.
  • Kastenmüller W; Würzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
  • Brown AS; Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Australia; Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia.
  • Hartland EL; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Australia; Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia; Department of Molecular and Translational Science, Monash University, Clayton, Australia.
  • van Driel IR; Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Australia; Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia.
  • Ng GZ; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Australia; Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Australia; Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia
  • Garbi N; Institute of Molecular Medicine and Experimental Immunology, Faculty of Medicine, University of Bonn, Bonn, Germany. Electronic address: ngarbi@uni-bonn.de.
Mucosal Immunol ; 17(5): 777-792, 2024 Oct.
Article en En | MEDLINE | ID: mdl-38750967
ABSTRACT
The immune response against Legionella longbeachae, a causative agent of the often-fatal Legionnaires' pneumonia, is poorly understood. Here, we investigated the specific roles of tissue-resident alveolar macrophages (AMs) and infiltrating phagocytes during infection with this pathogen. AMs were the predominant cell type that internalized bacteria 1 day after infection. A total of 3 and 5 days after infection, AM numbers were greatly reduced, whereas there was an influx of neutrophils and, later, monocyte-derived cells (MCs) into lung tissue. AMs carried greater numbers of viable L. longbeachae than neutrophils and MCs, which correlated with a higher capacity of L. longbeachae to translocate bacterial effector proteins required for bacterial replication into the AM cytosol. Cell ablation experiments demonstrated that AM promoted infection, whereas neutrophils and MC were required for efficient bacterial clearance. Interleukin (IL)-18 was important for interferon-γ production by IL-18R+ natural killer cells and T cells, which, in turn, stimulated reactive oxygen species-mediated bactericidal activity in neutrophils, resulting in the restriction of L. longbeachae infection. Ciliated bronchiolar epithelial cells also expressed IL-18R but did not play a role in IL-18-mediated L. longbeachae clearance. Our results have identified opposing innate functions of tissue-resident and infiltrating immune cells during L. longbeachae infection that may be manipulated to improve protective responses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón gamma / Macrófagos Alveolares / Especies Reactivas de Oxígeno / Legionella longbeachae / Neutrófilos Límite: Animals Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón gamma / Macrófagos Alveolares / Especies Reactivas de Oxígeno / Legionella longbeachae / Neutrófilos Límite: Animals Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos