Critical Role of Type 1 Cytokines in Controlling Initial Infection with Burkholderia mallei

• Published in: Infection and Immunity 2006-09, Vol.74 (9), p.5333-5340
• Main Authors: Rowland, Caroline A, 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
• Format: Article
• Language: English
• Subjects: Animals; Bacteriology; Biological and medical sciences; Burkholderia mallei; Burkholderia mallei - immunology; CD8-Positive T-Lymphocytes - immunology; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Cytokines - genetics; Cytokines - metabolism; Fundamental and applied biological sciences. Psychology; Glanders - genetics; Glanders - immunology; Host Response and Inflammation; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukins - genetics; Interleukins - metabolism; Killer Cells, Natural - immunology; Mice; Mice, Inbred BALB C; Mice, Knockout; Microbiology; Miscellaneous; Receptors, Antigen, T-Cell, gamma-delta - analysis; RNA, Messenger - analysis; RNA, Messenger - metabolism; Spleen - immunology; Spleen - microbiology; T-Lymphocytes - immunology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.02046-05

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.