In vitro modelling of bacterial pneumonia: a comparative analysis of widely applied complex cell culture models
Laure Mahieu1, Laurence Van Moll1, Linda De Vooght1
1Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Abstract:
Bacterial pneumonia greatly contributes to the disease burden and mortality of lower respiratory tract infections among all age groups and risk profiles. Therefore, laboratory modelling of bacterial pneumonia remains important for elucidating the complex host-pathogen interactions and to determine drug efficacy and toxicity. In vitro cell culture enables for the creation of high-throughput, specific disease models in a tightly controlled environment. Advanced human cell culture models specifically, can bridge the research gap between the classical two-dimensional cell models and animal models. This review provides an overview of the current status of the development of complex cellular in vitro models to study bacterial pneumonia infections, with a focus on air-liquid interface models, spheroid, organoid, and lung-on-a-chip models. For the wide scale, comparative literature search, we selected six clinically highly relevant bacteria (Pseudomonas aeruginosa, Mycoplasma pneumoniae, Haemophilus influenzae, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Staphylococcus aureus). We reviewed the cell lines that are commonly used, as well as trends and discrepancies in the methodology, ranging from cell infection parameters to assay read-outs. We also highlighted the importance of model validation and data transparency in guiding the research field towards more complex infection models.
Insights
Advanced in vitro models like lung-on-a-chip offer improved bacterial pneumonia research. These complex cell culture models enhance understanding of host-pathogen interactions and drug efficacy for lower respiratory tract infections.
Area of Science:
- Microbiology and Immunology
- Biomedical Engineering
- Cell Biology
Background:
- Bacterial pneumonia significantly impacts global health, necessitating robust laboratory models for research.
- Current research models struggle to fully replicate complex human lung environments for studying bacterial pneumonia.
- Advanced in vitro models are crucial for bridging the gap between traditional cell cultures and animal studies.
Approach:
- This review examines cutting-edge in vitro models for bacterial pneumonia, including air-liquid interface, spheroid, organoid, and lung-on-a-chip systems.
- A comprehensive literature search focused on six key bacterial pathogens: Pseudomonas aeruginosa, Mycoplasma pneumoniae, Haemophilus influenzae, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Staphylococcus aureus.
- Analysis includes common cell lines, methodological trends, and assay readouts in bacterial pneumonia modeling.
Key Points:
- Complex in vitro models provide controlled, high-throughput platforms for studying bacterial pneumonia.
- Lung-on-a-chip and organoid models show promise in mimicking human lung physiology for infection studies.
- Standardization and validation of these advanced models are critical for reliable results.
Conclusions:
- Advanced in vitro models are essential for accurate bacterial pneumonia research, offering detailed insights into host-pathogen dynamics.
- Further development and validation of complex cellular models will accelerate the discovery of new treatments for lower respiratory tract infections.
- Emphasis on data transparency and model validation is key to advancing the field of bacterial pneumonia in vitro modeling.
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