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[Novel model of replicative Legionella pneumophila lung infection in DBA/2 mice]
Yoshinori Kashimoto1, Yuichi Kurosaka, Yukie Karibe
1Daiichi Sankyo Co. Ltd., Biological Research Laboratories IV.
Abstract:
We present here a new model of Legionella pneumophila lung infection in DBA/2 mice. By intranasal inoculation with 106 colony-forming units of L. pneumophila strain suzuki serogoup 1, persistent non-lethal lung infection was established as reflected by the detection of more than 10(4) CFU/lung of the organism 14 days after infection. Treatment of mice with cyclophosphamide before infection enhanced bacterial replication in the lungs and all cyclophosphamide-treated mice experienced lethal infection. Histopathologically, the course of non-lethal lung infection was characterized by early response of neutrophiles, then monocyte/macrophages response in the alveoli with disease progression, and diffuse alveolar wall thickening with lymphocyte migration at later phase of infection. Transmission electron microscopic evaluation of the lungs confirmed that L. pneumophila located intracellularly within neutrophiles and infrequently intracellular bacteria were observed undergoing binary fission. Therefore, the mouse model of replicative L. pneumophila lung infection provides method for evaluating pathogenesis of L. pneumophila lung infection and antibacterial therapy.
Insights
This study establishes a new mouse model for Legionella pneumophila lung infection. The model aids in understanding bacterial pathogenesis and evaluating new therapies for Legionella pneumonia.
Area of Science:
- Microbiology
- Immunology
- Pathology
Context:
- Legionella pneumophila causes Legionnaires' disease, a severe form of pneumonia.
- DBA/2 mice are utilized to establish a persistent, non-lethal lung infection model.
- Cyclophosphamide treatment exacerbates infection, leading to lethal outcomes.
Purpose:
- To develop and characterize a novel mouse model for studying Legionella pneumophila lung infection.
- To investigate the histopathological and cellular responses during infection.
- To provide a platform for evaluating antibacterial therapies.
Summary:
- Intranasal inoculation of L. pneumophila in DBA/2 mice established a persistent lung infection.
- Histopathology revealed neutrophil and macrophage infiltration, followed by lymphocyte migration.
- Transmission electron microscopy confirmed intracellular bacterial location within neutrophils.
Impact:
- This replicative L. pneumophila lung infection model offers a valuable tool for pathogenesis research.
- It serves as a method for assessing the efficacy of antibacterial treatments against Legionella.
- The model facilitates a deeper understanding of host-pathogen interactions in pneumonia.
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