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Experimental Legionnaires' disease in SCID-Beige mice reconstituted with human leucocytes
A Williams1, B W McBride, G Hall
1Centre for Applied Microbiology and Research (CAMR), Porton Down, Salisbury, Wiltshire.
Abstract:
A new small animal model of experimental Legionnaires' disease is described in which the reconstitution of SCID-Beige mice with human peripheral blood leucocytes permits the in-vivo growth of Legionella pneumophila in the lungs of aerosol-challenged mice. Following infection, viable bacterial counts within the lungs of mice increased from 10(5) cfu/lung at the time of inoculation to a maximum of 10(10) cfu/lung by 48 h post-inoculation. Two types of disease were detected in the lungs of infected SCID-Beige mice. An acute exudative bronchiolitis and bronchopneumonia were seen in the most severely affected mice and, in the less severely affected mice, lesions of subacute or chronic disease were seen with thickening of alveolar walls and consolidation of lung tissue. Human cells did not appear to be involved directly in the pathology but were required for the establishment of infection. Immunohistological staining of lung tissue revealed substantial amounts of bacterial antigen distributed in a pattern similar to that seen in human Legionnaires' disease.
Insights
This study introduces a new SCID-Beige mouse model for Legionnaires' disease, allowing Legionella pneumophila growth in lungs. The model mimics human disease pathology and bacterial distribution patterns.
Area of Science:
- Immunology
- Infectious Diseases
- Animal Models
Background:
- Legionnaires' disease is a severe pneumonia caused by Legionella pneumophila.
- Existing animal models do not fully replicate human disease pathology or immune responses.
Purpose of the Study:
- To develop and characterize a novel small animal model for experimental Legionnaires' disease.
- To investigate the in-vivo growth and pathogenic potential of Legionella pneumophila in a humanized mouse model.
Main Methods:
- SCID-Beige mice were reconstituted with human peripheral blood leucocytes.
- Mice were aerosol-challenged with Legionella pneumophila.
- Lung tissues were analyzed for bacterial load, pathology, and antigen distribution.
Main Results:
- Successful in-vivo growth of Legionella pneumophila in the lungs of humanized mice was achieved.
- Bacterial counts increased significantly, reaching 10(10) cfu/lung by 48 hours post-inoculation.
- The model exhibited both acute exudative and subacute/chronic lung disease patterns, with bacterial antigen distribution resembling human cases.
Conclusions:
- The humanized SCID-Beige mouse model effectively supports Legionella pneumophila infection and disease development.
- This model provides a valuable tool for studying Legionnaires' disease pathogenesis and evaluating therapeutic strategies.