A model of immunity to Burkholderia pseudomallei

unique responses following immunization and acute lethal infection

G Ulett, J Labrooy, Bart Currie, J Barnes, Natkunam Ketheesan

Research output: Contribution to journalArticleResearchpeer-review

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 �LD50 (5 �103:CFU) of CL04 had significantly better survival and lower bacterial loads after LC compared to na� 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 na�-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. � 2005 Elsevier SAS. All rights reserved.
Original languageEnglish
Pages (from-to)1263-1275
Number of pages13
JournalMicrobes and Infection
Volume7
Issue number11-12
Publication statusPublished - 2005

Fingerprint

Burkholderia pseudomallei
Immunity
Immunization
Infection
Melioidosis
Cyclin-Dependent Kinases
Bacterial Load
Lethal Dose 50
Response Elements
Adaptive Immunity
Granulocyte-Macrophage Colony-Stimulating Factor
Oligonucleotide Array Sequence Analysis
Inbred C57BL Mouse
Libraries
Survival
Mortality
Genes

Cite this

Ulett, G ; Labrooy, J ; Currie, Bart ; Barnes, J ; Ketheesan, Natkunam. / A model of immunity to Burkholderia pseudomallei : unique responses following immunization and acute lethal infection. In: Microbes and Infection. 2005 ; Vol. 7, No. 11-12. pp. 1263-1275.
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A model of immunity to Burkholderia pseudomallei : unique responses following immunization and acute lethal infection. / Ulett, G; Labrooy, J; Currie, Bart; Barnes, J; Ketheesan, Natkunam.

In: Microbes and Infection, Vol. 7, No. 11-12, 2005, p. 1263-1275.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A model of immunity to Burkholderia pseudomallei

T2 - unique responses following immunization and acute lethal infection

AU - Ulett, G

AU - Labrooy, J

AU - Currie, Bart

AU - Barnes, J

AU - Ketheesan, Natkunam

PY - 2005

Y1 - 2005

N2 - 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 �LD50 (5 �103:CFU) of CL04 had significantly better survival and lower bacterial loads after LC compared to na� 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 na�-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. � 2005 Elsevier SAS. All rights reserved.

AB - 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 �LD50 (5 �103:CFU) of CL04 had significantly better survival and lower bacterial loads after LC compared to na� 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 na�-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. � 2005 Elsevier SAS. All rights reserved.

KW - cyclin dependent kinase

KW - protein BAD

KW - adaptive behavior

KW - animal experiment

KW - animal model

KW - article

KW - bacterial colonization

KW - bacterial strain

KW - bacterial virulence

KW - Burkholderia pseudomallei

KW - colony forming unit GM

KW - comparative study

KW - controlled study

KW - DNA microarray

KW - dose response

KW - gamma irradiation

KW - granulocyte

KW - immune response

KW - immunity

KW - immunization

KW - immunogenicity

KW - infection sensitivity

KW - mouse

KW - nonhuman

KW - priority journal

KW - screening

KW - survival

KW - Animals

KW - Bacterial Vaccines

KW - bcl-Associated Death Protein

KW - Blood

KW - Colony Count, Microbial

KW - Cross Reactions

KW - Cyclin-Dependent Kinase 5

KW - Disease Models, Animal

KW - Gene Expression Profiling

KW - Granulocyte-Macrophage Colony-Stimulating Factor

KW - Liver

KW - Melioidosis

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Oligonucleotide Array Sequence Analysis

KW - Spleen

KW - Survival Analysis

KW - Vaccination

KW - Vaccines, Attenuated

KW - Bacteria (microorganisms)

M3 - Article

VL - 7

SP - 1263

EP - 1275

JO - Microbes and Infection

JF - Microbes and Infection

SN - 1286-4579

IS - 11-12

ER -