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Dissection of a type I interferon pathway in controlling bacterial intracellular infection in mice |
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| Authors: | Lippmann Juliane Müller Holger C Naujoks Jan Tabeling Christoph Shin Sunny Witzenrath Martin Hellwig Katharina Kirschning Carsten J Taylor Gregory A Barchet Winfried Bauer Stefan Suttorp Norbert Roy Craig R Opitz Bastian |
| Affiliation: | 1. Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité Universit?tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.;2. Section of Microbial Pathogenesis, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.;3. Institute of Medical Microbiology, University Duisburg‐Essen, 45147 Essen, Germany.;4. Geriatric Research, Education, and Clinical Center, VA Medical Center, Durham, NC, USA.;5. Departments of Medicine, Molecular Genetics and Microbiology, and Immunolgy, Division of Geriatrics, and Center for the Study of Aging and Human Development, Durham, NC, USA.;6. Department of Cell Biology, Duke University Medical Center, Durham, NC, USA.;7. Institute of Clinical Chemistry and Pharmacology, University of Bonn, Sigmund Freud Strasse 35, 53127 Bonn, Germany.;8. Institute of Immunology, Philipps University Marburg, BMFZ, Hans‐Meerwein‐Str. 2, 35043 Marburg, Germany. |
| Abstract: | Defence mechanisms against intracellular bacterial pathogens are incompletely understood. Our study characterizes a type I IFN-dependent cell-autonomous defence pathway directed against Legionella pneumophila, an intracellular model organism and frequent cause of pneumonia. We show that macrophages infected with L. pneumophila produced IFNβ in a STING- and IRF3- dependent manner. Paracrine type I IFNs stimulated upregulation of IFN-stimulated genes and a cell-autonomous defence pathway acting on replicating and non-replicating Legionella within their specialized vacuole. Our infection experiments in mice lacking receptors for type I and/or II IFNs show that type I IFNs contribute to expression of IFN-stimulated genes and to bacterial clearance as well as resistance in L. pneumophila pneumonia in addition to type II IFN. Overall, our study shows that paracrine type I IFNs mediate defence against L. pneumophila, and demonstrates a protective role of type I IFNs in in vivo infections with intracellular bacteria. |
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