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Infektiologie Update 2018: 26. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG)

Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG)

04. - 06.10.2018, Wien, Österreich

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Antibiotic treatment-induced secondary IgA-deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia

Meeting Abstract

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  • Oliver H. Robak - Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany; Department of Medicine 1, Medical University of Vienna, Vienna, Austria
  • Markus M. Heimesaat - Institute of Microbiology and Hygiene, Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Andrey A. Kruglov - German Rheumatism Research Center – a Leibniz Institute, Berlin, Germany; A.N. Belozersky Institue of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Moscow, Russia; Department of immunology, Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia
  • Sandra Prepens - Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Justus Ninnemann - German Rheumatism Research Center – a Leibniz Institute, Berlin, Germany
  • Birgitt Gutbier - Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Katrin Reppe - Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Hubertus Hochrein - Department of Research Immunology, Bavarian Nordic GmbH, Martinsried, Germany
  • Mark Suter - Universität Zürich, Vetsuisse, Zürich, Switzerland
  • Carsten J. Kirschning - Institute of Medical Microbiology, University of Duisburg-Essen, Essen Germany
  • Veena Marathe - Institute of Medical Microbiology, University of Duisburg-Essen, Essen Germany
  • Jan Buer - Institute of Medical Microbiology, University of Duisburg-Essen, Essen Germany
  • Mathias W. Hornef - Institute of Medical Microbiology, University Hospital, RWTH Aachen, Germany
  • Markus Schnare - Institute of Immunology, University of Marburg, Marburg, Germany
  • Pascal Schneider - Department of Biochemistry, University of Lausanne, Epalinges, Switzerland
  • Martin Witzenrath - Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL), Germany
  • Stefan Bereswill - Institute of Microbiology and Hygiene, Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Ulrich Steinhoff - Institute of Medical Microbiology and Hygiene, University of Marburg, Marburg, Germany
  • Norbert Suttorp - Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL), Germany
  • Leif E. Sander - Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL), Germany
  • Catherine Chapu - Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Bastian Opitz - Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL), Germany

Infektiologie Update 2018. 26. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG). Wien, 04.-06.10.2018. Düsseldorf: German Medical Science GMS Publishing House; 2018. Doc18peg14

doi: 10.3205/18peg14, urn:nbn:de:0183-18peg141

Veröffentlicht: 8. Oktober 2018

© 2018 Robak et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Broad-spectrum antibiotics are widely used in patients on intensive care units (ICU), many of which develop hospital-acquired infections with Pseudomonas aeruginosa. Although preceding antimicrobial therapy is known as a major risk factor for P. aeruginosa-induced pneumonia, the underlying mechanisms remain incompletely understood. Here we demonstrate that depletion of the resident microbiota by broad-spectrum antibiotic treatment inhibits TLR-dependent production of a proliferation inducing ligand (APRIL), resulting in a secondary IgA deficiency in the lung in mice and human ICU patients. Microbiota-dependent local IgA contributes to early antibacterial defense against P. aeruginosa. Consequently, Pseudomonas-binding IgA purified from lamina propria culture or IgA hybridomas enhanced resistance of antibiotic-treated mice to P. aeruginosa infection after transnasal substation. Our study provides a mechanistic explanation for the well-documented risk of P. aeruginosa infection following antimicrobial therapy, and we propose local administration of IgA as a novel prophylactic strategy.