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  • A Model of Immunity to Burkholderia pseudomallei: Unique Responses following Immunization and Acute Lethal Infection

    Author(s)
    Ulett, GC
    Labrooy, JT
    Currie, BJ
    Barnes, JL
    Ketheesan, N
    Griffith University Author(s)
    Ulett, Glen C.
    Year published
    2005
    Metadata
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    Abstract
    Burkholderia pseudomallei, the etiological agent of melioidosis, causes significant mortality in endemic regions, but little is known regarding the immune mechanisms required for successful protective immunity. To establish a model of immunization that could be used to study this we screened a library of B. pseudomallei strains for immunogenicity in mice. BALB/c mice were immunized with test strains, and 2 weeks later were given a lethal challenge (LC) of virulent B. pseudomallei. Among 49 strains tested, a single strain, CL04, exhibited strong immunoprotective capacity. Interestingly, CL04 had been cultured from a patient ...
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    Burkholderia pseudomallei, the etiological agent of melioidosis, causes significant mortality in endemic regions, but little is known regarding the immune mechanisms required for successful protective immunity. To establish a model of immunization that could be used to study this we screened a library of B. pseudomallei strains for immunogenicity in mice. BALB/c mice were immunized with test strains, and 2 weeks later were given a lethal challenge (LC) of virulent B. pseudomallei. Among 49 strains tested, a single strain, CL04, exhibited strong immunoprotective capacity. Interestingly, CL04 had been cultured from a patient with chronic colonization of B. pseudomallei, which is a rare phenomenon. Mice immunized with 0.1 נLD50 (5 נ10^3 CFU) of CL04 had significantly better survival and lower bacterial loads after LC compared to naﶥ controls. Dose-response analysis demonstrated more robust immunity after higher immunizing doses, and bacterial inactivation by gamma irradiation diminished the protective effect, indicating a requirement for viable organism for immunity. CL04-induced immunity was demonstrated both in B. pseudomallei-susceptible BALB/c and -resistant C57BL/6 mice. We investigated the gene profile of CL04-induced immunity by analyzing responses to immunization using cDNA microarray. Unique responses involving granulocyte macrophage colony stimulating factor (GM-CSF), the proapoptotic regulator Bad and cyclin-dependent kinase (CDK5) were detected in immunized mice, but these responses were absent in naﶥ-LC mice. Further, responses differed between mouse strains, indicating dependence on host genetic background. This model will be useful in identifying elements of the immune response required for successful adaptive immunity against B. pseudomallei.
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    Journal Title
    Microbes and Infection
    Volume
    7
    Issue
    11
    Publisher URI
    http://www.sciencedirect.com/science/journal/12864579
    DOI
    https://doi.org/10.1016/j.micinf.2005.04.013
    Subject
    Microbiology
    Immunology
    Medical microbiology
    Medical bacteriology
    Publication URI
    http://hdl.handle.net/10072/25847
    Collection
    • Journal articles

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