Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia
Identifieur interne : 000718 ( Pmc/Checkpoint ); précédent : 000717; suivant : 000719Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia
Auteurs : Kristina Dietert [Allemagne] ; Birgitt Gutbier [Allemagne] ; Sandra M. Wienhold [Allemagne] ; Katrin Reppe [Allemagne] ; Xiaohui Jiang [Allemagne] ; Ling Yao [Allemagne] ; Catherine Chaput [Allemagne] ; Jan Naujoks [Allemagne] ; Markus Brack [Allemagne] ; Alexandra Kupke [Allemagne] ; Christin Peteranderl [Allemagne] ; Stephan Becker [Allemagne] ; Carolin Von Lachner [Allemagne] ; Nelli Baal [Allemagne] ; Hortense Slevogt [Allemagne] ; Andreas C. Hocke [Allemagne] ; Martin Witzenrath [Allemagne] ; Bastian Opitz [Allemagne] ; Susanne Herold [Allemagne] ; Holger Hackstein [Allemagne] ; Leif E. Sander [Allemagne] ; Norbert Suttorp [Allemagne] ; Achim D. Gruber [Allemagne]Source :
- PLoS ONE [ 1932-6203 ] ; 2017.
Abstract
Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress in other fields of tissue imaging, histopathology remains the most conclusive and practical read out tool for the descriptive and semiquantitative evaluation of mouse pneumonia and therapeutic interventions. Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by
Url:
DOI: 10.1371/journal.pone.0188251
PubMed: 29155867
PubMed Central: 5695780
Affiliations:
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PMC:5695780Le document en format XML
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</nlm:aff>
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<author><name sortKey="Witzenrath, Martin" sort="Witzenrath, Martin" uniqKey="Witzenrath M" first="Martin" last="Witzenrath">Martin Witzenrath</name>
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
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<author><name sortKey="Opitz, Bastian" sort="Opitz, Bastian" uniqKey="Opitz B" first="Bastian" last="Opitz">Bastian Opitz</name>
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
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<author><name sortKey="Herold, Susanne" sort="Herold, Susanne" uniqKey="Herold S" first="Susanne" last="Herold">Susanne Herold</name>
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
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<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
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<author><name sortKey="Hackstein, Holger" sort="Hackstein, Holger" uniqKey="Hackstein H" first="Holger" last="Hackstein">Holger Hackstein</name>
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<wicri:noRegion>Giessen</wicri:noRegion>
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<author><name sortKey="Sander, Leif E" sort="Sander, Leif E" uniqKey="Sander L" first="Leif E." last="Sander">Leif E. Sander</name>
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
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</nlm:aff>
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<author><name sortKey="Gruber, Achim D" sort="Gruber, Achim D" uniqKey="Gruber A" first="Achim D." last="Gruber">Achim D. Gruber</name>
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<author><name sortKey="Gutbier, Birgitt" sort="Gutbier, Birgitt" uniqKey="Gutbier B" first="Birgitt" last="Gutbier">Birgitt Gutbier</name>
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<author><name sortKey="Wienhold, Sandra M" sort="Wienhold, Sandra M" uniqKey="Wienhold S" first="Sandra M." last="Wienhold">Sandra M. Wienhold</name>
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<author><name sortKey="Reppe, Katrin" sort="Reppe, Katrin" uniqKey="Reppe K" first="Katrin" last="Reppe">Katrin Reppe</name>
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<author><name sortKey="Jiang, Xiaohui" sort="Jiang, Xiaohui" uniqKey="Jiang X" first="Xiaohui" last="Jiang">Xiaohui Jiang</name>
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chaput, Catherine" sort="Chaput, Catherine" uniqKey="Chaput C" first="Catherine" last="Chaput">Catherine Chaput</name>
<affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Naujoks, Jan" sort="Naujoks, Jan" uniqKey="Naujoks J" first="Jan" last="Naujoks">Jan Naujoks</name>
<affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Brack, Markus" sort="Brack, Markus" uniqKey="Brack M" first="Markus" last="Brack">Markus Brack</name>
<affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kupke, Alexandra" sort="Kupke, Alexandra" uniqKey="Kupke A" first="Alexandra" last="Kupke">Alexandra Kupke</name>
<affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Internal Medicine II, Section for Infectious Diseases, Universities Giessen & Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL) Giessen, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine II, Section for Infectious Diseases, Universities Giessen & Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL) Giessen</wicri:regionArea>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff004"><addr-line>Institute of Virology, Philipps University of Marburg, German Center for Infection Research (DZIF), TTU Emerging Infections, Marburg, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Virology, Philipps University of Marburg, German Center for Infection Research (DZIF), TTU Emerging Infections, Marburg</wicri:regionArea>
<placeName><region type="land" nuts="1">Hesse (Land)</region>
<region type="district" nuts="2">District de Giessen</region>
<settlement type="city">Marbourg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Peteranderl, Christin" sort="Peteranderl, Christin" uniqKey="Peteranderl C" first="Christin" last="Peteranderl">Christin Peteranderl</name>
<affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Internal Medicine II, Section for Infectious Diseases, Universities Giessen & Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL) Giessen, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine II, Section for Infectious Diseases, Universities Giessen & Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL) Giessen</wicri:regionArea>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name>
<affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Internal Medicine II, Section for Infectious Diseases, Universities Giessen & Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL) Giessen, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine II, Section for Infectious Diseases, Universities Giessen & Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL) Giessen</wicri:regionArea>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff004"><addr-line>Institute of Virology, Philipps University of Marburg, German Center for Infection Research (DZIF), TTU Emerging Infections, Marburg, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Virology, Philipps University of Marburg, German Center for Infection Research (DZIF), TTU Emerging Infections, Marburg</wicri:regionArea>
<placeName><region type="land" nuts="1">Hesse (Land)</region>
<region type="district" nuts="2">District de Giessen</region>
<settlement type="city">Marbourg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Von Lachner, Carolin" sort="Von Lachner, Carolin" uniqKey="Von Lachner C" first="Carolin" last="Von Lachner">Carolin Von Lachner</name>
<affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Septomics Research Center, Jena University Hospital, Jena, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Septomics Research Center, Jena University Hospital, Jena</wicri:regionArea>
<wicri:noRegion>Jena</wicri:noRegion>
<wicri:noRegion>Jena</wicri:noRegion>
<wicri:noRegion>Jena</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Baal, Nelli" sort="Baal, Nelli" uniqKey="Baal N" first="Nelli" last="Baal">Nelli Baal</name>
<affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Institute for Clinical Immunology and Transfusion Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), University Hospital Giessen und Marburg, Justus-Liebig-University Giessen, Giessen, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Clinical Immunology and Transfusion Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), University Hospital Giessen und Marburg, Justus-Liebig-University Giessen, Giessen</wicri:regionArea>
<wicri:noRegion>Giessen</wicri:noRegion>
<wicri:noRegion>Giessen</wicri:noRegion>
<wicri:noRegion>Giessen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Slevogt, Hortense" sort="Slevogt, Hortense" uniqKey="Slevogt H" first="Hortense" last="Slevogt">Hortense Slevogt</name>
<affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Septomics Research Center, Jena University Hospital, Jena, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Septomics Research Center, Jena University Hospital, Jena</wicri:regionArea>
<wicri:noRegion>Jena</wicri:noRegion>
<wicri:noRegion>Jena</wicri:noRegion>
<wicri:noRegion>Jena</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hocke, Andreas C" sort="Hocke, Andreas C" uniqKey="Hocke A" first="Andreas C." last="Hocke">Andreas C. Hocke</name>
<affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Witzenrath, Martin" sort="Witzenrath, Martin" uniqKey="Witzenrath M" first="Martin" last="Witzenrath">Martin Witzenrath</name>
<affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Opitz, Bastian" sort="Opitz, Bastian" uniqKey="Opitz B" first="Bastian" last="Opitz">Bastian Opitz</name>
<affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Herold, Susanne" sort="Herold, Susanne" uniqKey="Herold S" first="Susanne" last="Herold">Susanne Herold</name>
<affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Internal Medicine II, Section for Infectious Diseases, Universities Giessen & Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL) Giessen, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine II, Section for Infectious Diseases, Universities Giessen & Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL) Giessen</wicri:regionArea>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
<wicri:noRegion>Member of the German Center for Lung Research (DZL) Giessen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hackstein, Holger" sort="Hackstein, Holger" uniqKey="Hackstein H" first="Holger" last="Hackstein">Holger Hackstein</name>
<affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Institute for Clinical Immunology and Transfusion Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), University Hospital Giessen und Marburg, Justus-Liebig-University Giessen, Giessen, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Clinical Immunology and Transfusion Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), University Hospital Giessen und Marburg, Justus-Liebig-University Giessen, Giessen</wicri:regionArea>
<wicri:noRegion>Giessen</wicri:noRegion>
<wicri:noRegion>Giessen</wicri:noRegion>
<wicri:noRegion>Giessen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sander, Leif E" sort="Sander, Leif E" uniqKey="Sander L" first="Leif E." last="Sander">Leif E. Sander</name>
<affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Suttorp, Norbert" sort="Suttorp, Norbert" uniqKey="Suttorp N" first="Norbert" last="Suttorp">Norbert Suttorp</name>
<affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gruber, Achim D" sort="Gruber, Achim D" uniqKey="Gruber A" first="Achim D." last="Gruber">Achim D. Gruber</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Veterinary Pathology, Freie Universität Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress in other fields of tissue imaging, histopathology remains the most conclusive and practical read out tool for the descriptive and semiquantitative evaluation of mouse pneumonia and therapeutic interventions. Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by <italic>Streptococcus (S</italic>
.<italic>) pneumoniae</italic>
, <italic>Staphylococcus aureus</italic>
, <italic>Klebsiella pneumoniae</italic>
, <italic>Acinetobacter baumannii</italic>
, <italic>Legionella pneumophila</italic>
, <italic>Escherichia coli</italic>
, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with <italic>S</italic>
. <italic>pneumoniae</italic>
. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. We therefore identified core criteria for each model suitable for practical semiquantitative scoring systems that take into account the pathogen- and model-specific patterns of pneumonia. Other critical factors that affect experimental pathologies are discussed, including infectious dose, time kinetics, and the genetic background of the mouse strain. The substantial differences between the model-specific pathologies underscore the necessity of pathogen- and model-adapted criteria for the comparative quantification of experimental outcomes. These criteria also allow for the standardized validation and comparison of treatment strategies in preclinical models.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lode, Hm" uniqKey="Lode H">HM Lode</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Pletz, Mw" uniqKey="Pletz M">MW Pletz</name>
</author>
<author><name sortKey="Rohde, G" uniqKey="Rohde G">G Rohde</name>
</author>
<author><name sortKey="Schutte, H" uniqKey="Schutte H">H Schutte</name>
</author>
<author><name sortKey="Bals, R" uniqKey="Bals R">R Bals</name>
</author>
<author><name sortKey="Von Baum, H" uniqKey="Von Baum H">H von Baum</name>
</author>
<author><name sortKey="Welte, T" uniqKey="Welte T">T Welte</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hament, Jm" uniqKey="Hament J">JM Hament</name>
</author>
<author><name sortKey="Kimpen, Jl" uniqKey="Kimpen J">JL Kimpen</name>
</author>
<author><name sortKey="Fleer, A" uniqKey="Fleer A">A Fleer</name>
</author>
<author><name sortKey="Wolfs, Tf" uniqKey="Wolfs T">TF Wolfs</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lorente, L" uniqKey="Lorente L">L Lorente</name>
</author>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pugin, J" uniqKey="Pugin J">J Pugin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Feldman, C" uniqKey="Feldman C">C Feldman</name>
</author>
<author><name sortKey="Anderson, R" uniqKey="Anderson R">R Anderson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pletz, Mw" uniqKey="Pletz M">MW Pletz</name>
</author>
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</author>
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</author>
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</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Feikin, Dr" uniqKey="Feikin D">DR Feikin</name>
</author>
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</author>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jain, S" uniqKey="Jain S">S Jain</name>
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</author>
<author><name sortKey="Louie, J" uniqKey="Louie J">J Louie</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jefferson, T" uniqKey="Jefferson T">T Jefferson</name>
</author>
<author><name sortKey="Jones, Ma" uniqKey="Jones M">MA Jones</name>
</author>
<author><name sortKey="Doshi, P" uniqKey="Doshi P">P Doshi</name>
</author>
<author><name sortKey="Del Mar, Cb" uniqKey="Del Mar C">CB Del Mar</name>
</author>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Metersky, Ml" uniqKey="Metersky M">ML Metersky</name>
</author>
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</author>
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<author><name sortKey="File, Tm" uniqKey="File T">TM File</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sabria, M" uniqKey="Sabria M">M Sabria</name>
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</biblStruct>
<biblStruct><analytic><author><name sortKey="Vergis, En" uniqKey="Vergis E">EN Vergis</name>
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</biblStruct>
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</biblStruct>
<biblStruct><analytic><author><name sortKey="Chastre, J" uniqKey="Chastre J">J Chastre</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Joseph, Nm" uniqKey="Joseph N">NM Joseph</name>
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<author><name sortKey="Sistla, S" uniqKey="Sistla S">S Sistla</name>
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<author><name sortKey="Parija, Sc" uniqKey="Parija S">SC Parija</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Patil, Hv" uniqKey="Patil H">HV Patil</name>
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<author><name sortKey="Patil, Vc" uniqKey="Patil V">VC Patil</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ahmad, Ta" uniqKey="Ahmad T">TA Ahmad</name>
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<author><name sortKey="El Sayed, Lh" uniqKey="El Sayed L">LH El-Sayed</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jarvis, Wr" uniqKey="Jarvis W">WR Jarvis</name>
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<author><name sortKey="Munn, Vp" uniqKey="Munn V">VP Munn</name>
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<author><name sortKey="Highsmith, Ak" uniqKey="Highsmith A">AK Highsmith</name>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group><journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, CA USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">29155867</article-id>
<article-id pub-id-type="pmc">5695780</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0188251</article-id>
<article-id pub-id-type="publisher-id">PONE-D-17-27356</article-id>
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<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pulmonology</subject>
<subj-group><subject>Pneumonia</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Bacteria</subject>
<subj-group><subject>Streptococcus</subject>
<subj-group><subject>Pneumococcus</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Medical Microbiology</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
<subj-group><subject>Streptococcus</subject>
<subj-group><subject>Pneumococcus</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
<subj-group><subject>Streptococcus</subject>
<subj-group><subject>Pneumococcus</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Medical Microbiology</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Viruses</subject>
<subj-group><subject>RNA viruses</subject>
<subj-group><subject>Orthomyxoviruses</subject>
<subj-group><subject>Influenza viruses</subject>
<subj-group><subject>Influenza A virus</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Medical microbiology</subject>
<subj-group><subject>Microbial pathogens</subject>
<subj-group><subject>Viral pathogens</subject>
<subj-group><subject>Orthomyxoviruses</subject>
<subj-group><subject>Influenza viruses</subject>
<subj-group><subject>Influenza A virus</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and health sciences</subject>
<subj-group><subject>Pathology and laboratory medicine</subject>
<subj-group><subject>Pathogens</subject>
<subj-group><subject>Microbial pathogens</subject>
<subj-group><subject>Viral pathogens</subject>
<subj-group><subject>Orthomyxoviruses</subject>
<subj-group><subject>Influenza viruses</subject>
<subj-group><subject>Influenza A virus</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Viruses</subject>
<subj-group><subject>Viral pathogens</subject>
<subj-group><subject>Orthomyxoviruses</subject>
<subj-group><subject>Influenza viruses</subject>
<subj-group><subject>Influenza A virus</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Bacteria</subject>
<subj-group><subject>Klebsiella</subject>
<subj-group><subject>Klebsiella Pneumoniae</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Medical Microbiology</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
<subj-group><subject>Klebsiella</subject>
<subj-group><subject>Klebsiella Pneumoniae</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Bacterial Pathogens</subject>
<subj-group><subject>Klebsiella</subject>
<subj-group><subject>Klebsiella Pneumoniae</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Viruses</subject>
<subj-group><subject>RNA viruses</subject>
<subj-group><subject>Coronaviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Medical Microbiology</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Coronaviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Coronaviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Viruses</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Coronaviruses</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune Response</subject>
<subj-group><subject>Inflammation</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune Response</subject>
<subj-group><subject>Inflammation</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Diagnostic Medicine</subject>
<subj-group><subject>Signs and Symptoms</subject>
<subj-group><subject>Inflammation</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Signs and Symptoms</subject>
<subj-group><subject>Inflammation</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia</article-title>
<alt-title alt-title-type="running-head">Comparative histopathology of mouse models of acute pneumonia</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-5667-6750</contrib-id>
<name><surname>Dietert</surname>
<given-names>Kristina</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Software</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gutbier</surname>
<given-names>Birgitt</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wienhold</surname>
<given-names>Sandra M.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Reppe</surname>
<given-names>Katrin</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jiang</surname>
<given-names>Xiaohui</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yao</surname>
<given-names>Ling</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chaput</surname>
<given-names>Catherine</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Naujoks</surname>
<given-names>Jan</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brack</surname>
<given-names>Markus</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kupke</surname>
<given-names>Alexandra</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff004"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Peteranderl</surname>
<given-names>Christin</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Becker</surname>
<given-names>Stephan</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff004"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>von Lachner</surname>
<given-names>Carolin</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Baal</surname>
<given-names>Nelli</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff006"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Slevogt</surname>
<given-names>Hortense</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hocke</surname>
<given-names>Andreas C.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Witzenrath</surname>
<given-names>Martin</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Opitz</surname>
<given-names>Bastian</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Herold</surname>
<given-names>Susanne</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hackstein</surname>
<given-names>Holger</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff006"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sander</surname>
<given-names>Leif E.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Suttorp</surname>
<given-names>Norbert</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gruber</surname>
<given-names>Achim D.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
</contrib-group>
<aff id="aff001"><label>1</label>
<addr-line>Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany</addr-line>
</aff>
<aff id="aff002"><label>2</label>
<addr-line>Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany</addr-line>
</aff>
<aff id="aff003"><label>3</label>
<addr-line>Department of Internal Medicine II, Section for Infectious Diseases, Universities Giessen & Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL) Giessen, Germany</addr-line>
</aff>
<aff id="aff004"><label>4</label>
<addr-line>Institute of Virology, Philipps University of Marburg, German Center for Infection Research (DZIF), TTU Emerging Infections, Marburg, Germany</addr-line>
</aff>
<aff id="aff005"><label>5</label>
<addr-line>Septomics Research Center, Jena University Hospital, Jena, Germany</addr-line>
</aff>
<aff id="aff006"><label>6</label>
<addr-line>Institute for Clinical Immunology and Transfusion Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), University Hospital Giessen und Marburg, Justus-Liebig-University Giessen, Giessen, Germany</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Jeyaseelan</surname>
<given-names>Samithamby</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1"><addr-line>Louisiana State University, UNITED STATES</addr-line>
</aff>
<author-notes><fn fn-type="COI-statement" id="coi001"><p><bold>Competing Interests: </bold>
The authors have declared that no competing interests exist.</p>
</fn>
<corresp id="cor001">* E-mail: <email>achim.gruber@fu-berlin.de</email>
</corresp>
</author-notes>
<pub-date pub-type="epub"><day>20</day>
<month>11</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="collection"><year>2017</year>
</pub-date>
<volume>12</volume>
<issue>11</issue>
<elocation-id>e0188251</elocation-id>
<history><date date-type="received"><day>21</day>
<month>7</month>
<year>2017</year>
</date>
<date date-type="accepted"><day>5</day>
<month>11</month>
<year>2017</year>
</date>
</history>
<permissions><copyright-statement>© 2017 Dietert et al</copyright-statement>
<copyright-year>2017</copyright-year>
<copyright-holder>Dietert et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="pone.0188251.pdf"></self-uri>
<abstract><p>Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress in other fields of tissue imaging, histopathology remains the most conclusive and practical read out tool for the descriptive and semiquantitative evaluation of mouse pneumonia and therapeutic interventions. Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by <italic>Streptococcus (S</italic>
.<italic>) pneumoniae</italic>
, <italic>Staphylococcus aureus</italic>
, <italic>Klebsiella pneumoniae</italic>
, <italic>Acinetobacter baumannii</italic>
, <italic>Legionella pneumophila</italic>
, <italic>Escherichia coli</italic>
, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with <italic>S</italic>
. <italic>pneumoniae</italic>
. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. We therefore identified core criteria for each model suitable for practical semiquantitative scoring systems that take into account the pathogen- and model-specific patterns of pneumonia. Other critical factors that affect experimental pathologies are discussed, including infectious dose, time kinetics, and the genetic background of the mouse strain. The substantial differences between the model-specific pathologies underscore the necessity of pathogen- and model-adapted criteria for the comparative quantification of experimental outcomes. These criteria also allow for the standardized validation and comparison of treatment strategies in preclinical models.</p>
</abstract>
<funding-group><funding-statement>This work was supported by the German Research Foundation (DFG) SFB-TR 84 (<ext-link ext-link-type="uri" xlink:href="https://www.sfb-tr84.de/">https://www.sfb-tr84.de/</ext-link>
) A1, A5 (to B.O.), B2 (to S.H.), B3 (to H.H), C3, C6 (to M.W.), C8 (to L.E.S), Z1a (to A.C.H.), Z1b (to A.D.G.), DFG KFO 309 (<ext-link ext-link-type="uri" xlink:href="http://www.kfo309.de/">http://www.kfo309.de/</ext-link>
) P2 (to S.B., S.H. and C.P.), P8 (to S.H.), DFG SFB-1021 (<ext-link ext-link-type="uri" xlink:href="http://www.sfb1021.de/">http://www.sfb1021.de/</ext-link>
) C5 (to S.H.), EXC147 (<ext-link ext-link-type="uri" xlink:href="http://www.eccps.de/">http://www.eccps.de/</ext-link>
) (to S.H.) and the excellence graduate school Jena School for Microbial Communication (JSMC, to H.S.)(<ext-link ext-link-type="uri" xlink:href="http://www.jsmc.uni-jena.de">http://www.jsmc.uni-jena.de</ext-link>
). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts><fig-count count="11"></fig-count>
<table-count count="2"></table-count>
<page-count count="25"></page-count>
</counts>
<custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name>
<meta-value>All relevant data are within the paper.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes><title>Data Availability</title>
<p>All relevant data are within the paper.</p>
</notes>
</front>
</pmc>
<affiliations><list><country><li>Allemagne</li>
</country>
<region><li>Berlin</li>
<li>District de Giessen</li>
<li>Hesse (Land)</li>
</region>
<settlement><li>Berlin</li>
<li>Marbourg</li>
</settlement>
</list>
<tree><country name="Allemagne"><region name="Berlin"><name sortKey="Dietert, Kristina" sort="Dietert, Kristina" uniqKey="Dietert K" first="Kristina" last="Dietert">Kristina Dietert</name>
</region>
<name sortKey="Baal, Nelli" sort="Baal, Nelli" uniqKey="Baal N" first="Nelli" last="Baal">Nelli Baal</name>
<name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name>
<name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name>
<name sortKey="Brack, Markus" sort="Brack, Markus" uniqKey="Brack M" first="Markus" last="Brack">Markus Brack</name>
<name sortKey="Chaput, Catherine" sort="Chaput, Catherine" uniqKey="Chaput C" first="Catherine" last="Chaput">Catherine Chaput</name>
<name sortKey="Gruber, Achim D" sort="Gruber, Achim D" uniqKey="Gruber A" first="Achim D." last="Gruber">Achim D. Gruber</name>
<name sortKey="Gutbier, Birgitt" sort="Gutbier, Birgitt" uniqKey="Gutbier B" first="Birgitt" last="Gutbier">Birgitt Gutbier</name>
<name sortKey="Hackstein, Holger" sort="Hackstein, Holger" uniqKey="Hackstein H" first="Holger" last="Hackstein">Holger Hackstein</name>
<name sortKey="Herold, Susanne" sort="Herold, Susanne" uniqKey="Herold S" first="Susanne" last="Herold">Susanne Herold</name>
<name sortKey="Hocke, Andreas C" sort="Hocke, Andreas C" uniqKey="Hocke A" first="Andreas C." last="Hocke">Andreas C. Hocke</name>
<name sortKey="Jiang, Xiaohui" sort="Jiang, Xiaohui" uniqKey="Jiang X" first="Xiaohui" last="Jiang">Xiaohui Jiang</name>
<name sortKey="Kupke, Alexandra" sort="Kupke, Alexandra" uniqKey="Kupke A" first="Alexandra" last="Kupke">Alexandra Kupke</name>
<name sortKey="Kupke, Alexandra" sort="Kupke, Alexandra" uniqKey="Kupke A" first="Alexandra" last="Kupke">Alexandra Kupke</name>
<name sortKey="Naujoks, Jan" sort="Naujoks, Jan" uniqKey="Naujoks J" first="Jan" last="Naujoks">Jan Naujoks</name>
<name sortKey="Opitz, Bastian" sort="Opitz, Bastian" uniqKey="Opitz B" first="Bastian" last="Opitz">Bastian Opitz</name>
<name sortKey="Peteranderl, Christin" sort="Peteranderl, Christin" uniqKey="Peteranderl C" first="Christin" last="Peteranderl">Christin Peteranderl</name>
<name sortKey="Reppe, Katrin" sort="Reppe, Katrin" uniqKey="Reppe K" first="Katrin" last="Reppe">Katrin Reppe</name>
<name sortKey="Sander, Leif E" sort="Sander, Leif E" uniqKey="Sander L" first="Leif E." last="Sander">Leif E. Sander</name>
<name sortKey="Slevogt, Hortense" sort="Slevogt, Hortense" uniqKey="Slevogt H" first="Hortense" last="Slevogt">Hortense Slevogt</name>
<name sortKey="Suttorp, Norbert" sort="Suttorp, Norbert" uniqKey="Suttorp N" first="Norbert" last="Suttorp">Norbert Suttorp</name>
<name sortKey="Von Lachner, Carolin" sort="Von Lachner, Carolin" uniqKey="Von Lachner C" first="Carolin" last="Von Lachner">Carolin Von Lachner</name>
<name sortKey="Wienhold, Sandra M" sort="Wienhold, Sandra M" uniqKey="Wienhold S" first="Sandra M." last="Wienhold">Sandra M. Wienhold</name>
<name sortKey="Witzenrath, Martin" sort="Witzenrath, Martin" uniqKey="Witzenrath M" first="Martin" last="Witzenrath">Martin Witzenrath</name>
<name sortKey="Yao, Ling" sort="Yao, Ling" uniqKey="Yao L" first="Ling" last="Yao">Ling Yao</name>
</country>
</tree>
</affiliations>
</record>
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