Critical Role of Type 1 Cytokines in Controlling Initial Infection with Burkholderia mallei
2006
Bostwick, Caroline A. Rowland | Lertmemongkolchai, Ganjana | Bancroft, Alison | Haque, Ashraful | Lever, M Stephen | Griffin, Kate F. | Jackson, Matthew C. | Nelson, Michelle | O'Garra, Anne | Grencis, Richard | Bancroft, Gregory J. | Lukaszewski, Roman A.
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.
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