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

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.

Factor XI deficiency is not associated with an increased risk of pneumonia and pneumonia‐related mortality

“…While murine models mirror human pathologies in many aspects, there are substantial differences between human and mouse as well as among different mouse models for acute pneumonia, for instance. These can be attributed to the infectious dose, virulence of the pathogen, therapeutic interventions, etc …”

“…These can be attributed to the infectious dose, virulence of the pathogen, therapeutic interventions, etc. 22 TA B L E 2 Descriptive statistics, incidence density rate and crude HR for the association of FXI deficiency with pneumonia (any) and pneumonia requiring hospitalization (a proxy of pneumonia severity)…”

Endothelial–platelet interactions in influenza‐induced pneumonia: A potential therapeutic target

“…When analysed by histopathology, infected mice show pulmonary oedema and inflammatory cell infiltrations (Figure 1, see also ref. Dietert et al (2017)). In PR8 H1N1-infected mice, we could demonstrate many of the pathological findings also found in humans: oedema, bleeding and leucocyte infiltration in to the alveolar lumen, as well as exudates with dead cells in the bronchioli (Figure 1c, d and F I G U R E 2 Ultrastructure of lung alveolar tissue from non-infected, healthy and influenza A PR8 H1N1-infected mice 3 days post infection by transmission electron microscopy.…”

The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella pneumoniae Infection in the Lung

“…It is estimated that more than 150 million cases occur annually among children under 5 years old, leading to approximately 2 million deaths each year ( 1 ). Pneumonia is a lower respiratory tract disease characterized by an intense inflammatory response, which results in increased lung edema, loss of respiratory area, and can lead to respiratory impairment and death ( 2 – 4 ). It can be caused by several pathogens, such as virus, fungi, and bacteria.…”