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PLoS One. 2017 Nov 20;12(11):e0188251. doi: 10.1371/journal.pone.0188251. eCollection 2017.

Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia.

Author information

1
Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
2
Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
3
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.
4
Institute of Virology, Philipps University of Marburg, German Center for Infection Research (DZIF), TTU Emerging Infections, Marburg, Germany.
5
Septomics Research Center, Jena University Hospital, Jena, Germany.
6
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.

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 Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. pneumoniae. 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.

PMID:
29155867
PMCID:
PMC5695780
DOI:
10.1371/journal.pone.0188251
[Indexed for MEDLINE]
Free PMC Article

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