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Aerosol infection of mice with Bordetella pertussis
Abstract:
Aerosol inhalation of Bordetella pertussis Tohama phase I resulted in a reproducible and uniform infection of mice (strain DDY or ICR). Mice in groups of 10 exposed for 30 min to aerosols generated from bacterial suspensions of 10(9) and 10(10) organisms per ml resulted in mean bacterial counts of 2.3 (+/- 0.3) X 10(4) and 1.0 (+/- 0.3) X 10(5) colony-forming units, respectively, in the lung of each animal. Subsequent studies using a 30-min aerosol inoculation of ICR mice with 2 X 10(9) bacterial cells per ml showed: (i) B. pertussis cells reached a maximum of about 10(7) colony-forming units per lung 14 days after inhalation. (ii) Deaths (10 to 100%, depending on mouse age) occurred 10 to 14 days after exposure. (iii) The lung weight and the leukocyte count increased from basal values of 100 mg and 10(4) leukocytes per mm3 to a plateau of 950 mg and 1.95 X 10(5) leukocytes per mm3, respectively, 14 days after challenge. (iv) There was a significantly reduced rate of body weight gain by infected mice compared to noninfected mice. (v) With mortality as the criterion for disease, susceptibility varied with the age of mice as follows: 10 days old greater than 18 greater than 28 greater than 49. (vi) Bacteria were associated with ciliated respiratory epithelial cells by scanning electron microscopy.
Insights
Aerosolized Bordetella pertussis infection in mice causes significant lung pathology, increased mortality, and weight loss. Susceptibility to pertussis infection varies with mouse age, with younger mice being more vulnerable.
Area of Science:
- Microbiology
- Immunology
- Animal Models
Background:
- Pertussis, or whooping cough, is a highly contagious respiratory disease caused by Bordetella pertussis.
- Establishing reproducible animal models is crucial for understanding pertussis pathogenesis and developing effective interventions.
Purpose of the Study:
- To develop and characterize a reproducible mouse model of Bordetella pertussis infection via aerosol inhalation.
- To investigate the dose-dependent effects of B. pertussis inhalation on infection dynamics, host response, and mortality.
- To assess the influence of host age on susceptibility to B. pertussis infection.
Main Methods:
- Mice (DDY or ICR strains) were exposed to aerosols of B. pertussis Tohama phase I at varying concentrations.
- Bacterial load in lungs, mortality rates, lung weight, leukocyte counts, and body weight gain were monitored over time.
- Scanning electron microscopy was used to visualize bacterial association with respiratory epithelial cells.
Main Results:
- Aerosol inhalation of B. pertussis led to uniform and reproducible lung infections in mice.
- Infected mice exhibited increased lung weight, elevated leukocyte counts, and reduced body weight gain.
- Mortality rates ranged from 10-100% and were significantly influenced by mouse age, with younger mice (10 days old) being most susceptible.
- B. pertussis was observed to associate with ciliated respiratory epithelial cells.
Conclusions:
- Aerosol inhalation of B. pertussis provides a robust model for studying pertussis in mice.
- The model effectively mimics key aspects of human pertussis infection, including respiratory pathology and age-dependent susceptibility.
- This model is valuable for future research into pertussis pathogenesis and the evaluation of vaccines and therapeutics.