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A model of immunity to Burkholderia pseudomallei: unique responses following immunization and acute lethal infection

Ulett, Glen C., Labrooy, Justin T., Currie, Bart J., Barnes, Jodie L. and Ketheesan, Natkunam (2005). A model of immunity to Burkholderia pseudomallei: unique responses following immunization and acute lethal infection. Microbes and Infection: a journal on infectious agents and host defenses,7(11-Dec):1263-1275.

Document type: Journal Article
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IRMA ID 10139xPUB111
Title A model of immunity to Burkholderia pseudomallei: unique responses following immunization and acute lethal infection
Author Ulett, Glen C.
Labrooy, Justin T.
Currie, Bart J.
Barnes, Jodie L.
Ketheesan, Natkunam
Journal Name Microbes and Infection: a journal on infectious agents and host defenses
Publication Date 2005
Volume Number 7
Issue Number 11-Dec
ISSN 1286-4579   (check CDU catalogue open catalogue search in new window)
Start Page 1263
End Page 1275
Total Pages 13
Place of Publication France
Publisher Elsevier Masson
Field of Research 0605 - Microbiology
1108 - Medical Microbiology
1107 - Immunology
HERDC Category C1 - Journal Article (DEST)
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 with chronic colonization of B. pseudomallei, which is a rare phenomenon. Mice immunized with 0.1 x LD50 (5 x 10(3) CFU) of CL04 had significantly better survival and lower bacterial loads after LC compared to naive 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 macrophaloe 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 naive-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.
Keywords burkholderia pseudomallei
melioidosis
immunization
DOI http://dx.doi.org/10.1016/j.micinf.2005.04.013   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
 
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