Best Practices in the Development and Use of Experimental Models of Bacterial Pneumonia: An Official American Thoracic Society Workshop Report

Abstract

The global incidence of respiratory infectious diseases caused by bacteria continues to increase, with acute lower respiratory tract infections contributing to significant morbidity and mortality. Preclinical models designed to investigate such respiratory bacterial diseases are of utmost importance to decipher their pathogenesis and develop novel targets for intervention and treatment. Animal models offer the powerful ability to investigate different pneumonia types at varying stages of infection and disease. However, the same models can promote important variations in outcome, potentially confounding scientific understanding in the field. Therefore, an expert panel was convened to deliberate best practices in animal models of bacterial pneumonia to identify validated methodologies and acknowledge limitations in the use of animal and non-animal models in this field of study. Herein, we summarize this American Thoracic Society workshop on animal models of bacterial pneumonia. This workshop further includes review of non-animal complementary or alternative models for studying bacterial pneumonia. Emphasis was placed on discussion of bacterial pathogens that frequently cause community- and hospital-acquired pneumonia, highlighting key aspects in modeling infection. Animal models discussed included small and large animals, based on their strengths. Finally and most importantly, the ethical considerations in the use of animal modeling for the study of bacterial lung infections was discussed. This workshop report is intended to provide insights to investigators in the field and may serve as a starting point for formal recommendations in the future.

Keywords: animals; bacterial infection; ethical considerations; experimental models; lungs.

Figure 1.

Important factors in the development and use of models to study pneumonia. Careful attention is paid to specific factors involved in pneumonia modeling, which include the organisms, host factors, specific methodology, and outcome measures. In addition, within each of these factors, ethical consideration, utility of complementary models, human relevance, and practical logistics are important. Created with BioRender.com.

Figure 2.

Complementary models for the study of bacterial pneumonia. (A) Selected historical highlights of in vitro cell and organ culture relevant to infectious disease. (B) Illustration of complementary models for pneumonia research and development. ATII = type 2 alveolar epithelium; PCLS = precision-cut lung slice. Panel (A) created with BioRender.com.