A multiple comorbidities mouse lung infection model in ApoE‑deficient mice
Benjamin Bartlett1,2, Silvia Lee1,3, Herbert P Ludewick1,4
1Department of Advanced Clinical and Translational Cardiovascular Imaging, Harry Perkins Institute of Medical Research, Perth, Western Australia 6150, Australia.
This study shows that pneumonia exacerbates inflammation in mice with atherosclerosis. This new model helps understand how infections like pneumonia increase cardiovascular disease risk.
Area of Science:
- Cardiovascular Science
- Infectious Disease Research
- Inflammation Biology
Background:
- Acute pneumonia involves intense inflammation, a key factor in atherosclerosis progression.
- Pre-existing atherosclerotic inflammation may influence pneumonia severity and risk.
- Understanding the interplay between infection and cardiovascular disease is crucial.
Purpose of the Study:
- To investigate respiratory and systemic inflammation in a murine model of atherosclerosis with pneumonia.
- To establish a reliable model for studying pneumonia in the context of cardiovascular disease.
Main Methods:
- Atherosclerotic C57Bl/6 ApoE-/- mice on a high-fat diet were inoculated with Streptococcus pneumoniae (TIGR4 strain).
- Lung inflammation was assessed using magnetic resonance imaging (MRI) and positron emission tomography (PET) up to 28 days post-inoculation.
- Systemic inflammation was evaluated via ELISA, Luminex assay, and real-time PCR.
Main Results:
- Pneumonia induction led to persistent lung inflammation, including infiltrate and consolidation, visible on MRI up to 28 days.
- Positron emission tomography revealed increased FDG uptake in lungs, indicating ongoing inflammation.
- Elevated inflammatory markers (IL-1β, IL-6, CCL3) and a pneumococcal-specific IgG response were observed.
Conclusions:
- The developed murine model effectively simulates pneumonia in an atherosclerotic setting, highlighting persistent inflammation.
- This model serves as a valuable tool for elucidating the link between infectious inflammation and cardiovascular disease risk.
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