Journal Article

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

Brack, Markus, Opitz, Bastian, Gutbier, Birgitt, Hocke, Andreas C., Gruber, Achim D., Slevogt, Hortense, Witzenrath, Martin, Baal, Nelli, Suttorp, Norbert, Wienhold, Sandra M., Becker, Stephan, von Lachner, Carolin, Jiang, Xiaohui, Chaput, Catherine, Naujoks, Jan, Sander, Leif E., Kupke, Alexandra, Dietert, Kristina, Herold, Susanne, Hackstein, Holger, Peteranderl, Christin, Yao, Ling, Reppe, Katrin

2017

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acinetobacter baumannii - pathogenicity / Acinetobacter baumannii - physiology / Animal models / Animal tissues / Animals / Bacterial pneumonia / Biology and Life Sciences / Causes of / Coronaviridae / Coronaviruses / Criteria / Cytokines / Disease Models, Animal / Drug therapy / E coli / Escherichia coli - pathogenicity / Escherichia coli - physiology / Female / Gene expression / Histopathology / Hospitals / Host Specificity / Humans / Immunohistochemistry / Immunology / Infectious diseases / Inflammation / Influenza / Influenza A / Influenza A virus - pathogenicity / Influenza A virus - physiology / Internal medicine / Kinetics / Klebsiella / Klebsiella pneumoniae - pathogenicity / Klebsiella pneumoniae - physiology / Legionella / Legionella pneumophila - pathogenicity / Legionella pneumophila - physiology / Legionnaires' disease bacterium / Lesions / Lung - microbiology / Lung - pathology / Lung - virology / Lungs / Medical treatment / Medicine / Medicine and Health Sciences / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Middle East Respiratory Syndrome Coronavirus - pathogenicity / Middle East Respiratory Syndrome Coronavirus - physiology / Mortality / Pathogenic microorganisms / Pathogens / Pathology / Physiological aspects / Physiology / Pneumonia / Pneumonia, Bacterial - genetics / Pneumonia, Bacterial - microbiology / Pneumonia, Bacterial - pathology / Pneumonia, Bacterial - physiopathology / Pneumonia, Viral - genetics / Pneumonia, Viral - pathology / Pneumonia, Viral - physiopathology / Pneumonia, Viral - virology / Respiratory diseases / Species Specificity / Staphylococcus aureus - pathogenicity / Staphylococcus aureus - physiology / Streptococcus infections / Streptococcus pneumoniae - pathogenicity / Streptococcus pneumoniae - physiology / Superinfection / Therapeutic applications / Viral infections / Virology / Viruses