Critical role of type 1 cytokines in controlling initial infection with Burkholderia mallei

Caroline A. Rowland, Ganjana Lertmemongkolchai, Alison Bancroft, Ashraful Haque, M. Stephen Lever, Kate F. Griffin, Matthew C. Jackson, Michelle Nelson, Anne O'Garra, Richard Grencis, Gregory J. Bancroft, Roman A. Lukaszewski

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Burkholderia mallei is a gram-negative bacterium which causes the potentially fatal disease glanders in humans; however, there is little information concerning cell-mediated immunity to this pathogen. The role of gamma interferon (IFN-γ) during B. mallei infection was investigated using a disease model in which infected BALB/c mice normally die between 40 and 60 days postinfection. IFN-γ knockout mice infected with B. mallei died within 2 to 3 days after infection, and there was uncontrolled bacterial replication in several organs, demonstrating the essential role of IFN-γ in the innate immune response to this pathogen. Increased levels of IFN-γ, interleukin-6 (IL-6), and monocyte chemoattractant protein 1 were detected in the sera of immunocompetent mice in response to infection, and splenic mRNA expression of IFN-γ, IL-6, IL-12p35, and IL-27 was elevated 24 h postinfection. The effects of IL-18, IL-27, and IL-12 on stimulation of the rapid IFN-γ production were investigated in vitro by analyzing IFN-γ production in the presence of heat-killed B. mallei. IL-12 was essential for IFN-γ production in vitro; IL-18 was also involved in induction of IFN-γ, but IL-27 was not required for IFN-γ production in response to heat-killed B. mallei. The main cellular sources of IFN-γ were identified in vitro as NK cells, CD8+ T cells, and TCRγδ T cells. Our data show that B. mallei is susceptible to cell-mediated immune responses which promote expression of type 1 cytokines. This suggests that development of effective vaccines against glanders should target the production of IFN-γ. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
    Original languageEnglish
    Pages (from-to)5333-5340
    Number of pages7
    JournalInfection and immunity
    Volume74
    Issue number9
    DOIs
    Publication statusPublished - Sept 2006

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