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Published on: October 16, 2013
Model of differential susceptibility to mucosal Burkholderia pseudomallei infection
Boping Liu1, Ghee Chong Koo, Eu Hian Yap
1Department of Biochemistry. Department of Microbiology, National University of Singapore, Singapore 119260.
Abstract:
Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease with protean clinical manifestations. The major route of infection is thought to be through subcutaneous inoculation of contaminated soil and water, although ingestion and inhalation of contaminated aerosols are also possible. This study examines infection through the intranasal route in a murine model to mimic infection through inhalation. Two strains of mice, C57BL/6 and BALB/c, exhibit differential susceptibilities to the infection, with the C57BL/6 mice being considerably more resistant. To examine host factors that could contribute to this difference, bacterial loads and cytokine profiles in the two strains of mice were compared. We found that infected BALB/c mice exhibited higher bacterial loads in the lung and spleen and that they produced significantly higher levels of gamma interferon (IFN-gamma) in the serum than C57BL/6 mice. Although tumor necrosis factor alpha and interleukin-1 could be detected in the nasal washes and sera of both strains of mice, the production in serum was transient and much lower than that of IFN-gamma. C57BL/6 mice also exhibited memory responses to bacteria upon reinfection, with the production of serum immunoglobulin G (IgG) and mucosal IgA antibodies. Thus, it is possible that the production of systemic and mucosal antibodies is important for protection against disease in C57BL/6 mice.
Insights
BALB/c mice are more susceptible to Burkholderia pseudomallei infection than C57BL/6 mice, showing higher bacterial loads and increased gamma interferon (IFN-γ) production. C57BL/6 mice develop protective antibody responses, suggesting their importance in melioidosis resistance.
Area of Science:
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Melioidosis, caused by Burkholderia pseudomallei, presents diverse clinical symptoms.
- Infection typically occurs via contaminated soil/water, but inhalation is also a significant route.
- Understanding host resistance factors is crucial for managing melioidosis.
Purpose of the Study:
- To investigate host susceptibility differences in murine models of intranasal Burkholderia pseudomallei infection.
- To compare bacterial loads and cytokine profiles between C57BL/6 and BALB/c mice.
- To identify immune mechanisms contributing to differential resistance against melioidosis.
Main Methods:
- Intranasal inoculation of Burkholderia pseudomallei in C57BL/6 and BALB/c mice.
- Quantification of bacterial loads in lung and spleen.
- Measurement of serum and nasal wash cytokine levels (IFN-γ, TNF-α, IL-1).
- Assessment of antibody responses (IgG, IgA) upon secondary infection.
Main Results:
- BALB/c mice exhibited significantly higher bacterial loads in the lung and spleen compared to C57BL/6 mice.
- Infected BALB/c mice produced higher levels of serum gamma interferon (IFN-γ).
- C57BL/6 mice demonstrated memory responses with serum IgG and mucosal IgA antibody production upon reinfection.
Conclusions:
- Differential susceptibility to Burkholderia pseudomallei infection exists between C57BL/6 and BALB/c mice.
- Higher IFN-γ production in BALB/c mice correlates with increased susceptibility.
- Systemic and mucosal antibody production may play a critical role in C57BL/6 mice's resistance to melioidosis.
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