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Infection and Immunity, September 2006, p. 5333-5340, Vol. 74, No. 9
0019-9567/06/$08.00+0     doi:10.1128/IAI.02046-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

Dstl, Porton Down, Salisbury, SP4 0JQ, United Kingdom,¹ Department of Clinical Immunology, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002 Thailand,² University of Manchester, Manchester, United Kingdom,³ London School of Hygiene and Tropical Medicine, Keppel St., London, United Kingdom,⁴ Medical Research Institute, Mill Hill, London, United Kingdom⁵

Received 20 December 2005/ Returned for modification 7 February 2006/ Accepted 14 April 2006

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-) 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- 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- in the innate immune response to this pathogen. Increased levels of IFN-, 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-, 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- production were investigated in vitro by analyzing IFN- production in the presence of heat-killed B. mallei. IL-12 was essential for IFN- production in vitro; IL-18 was also involved in induction of IFN-, but IL-27 was not required for IFN- production in response to heat-killed B. mallei. The main cellular sources of IFN- were identified in vitro as NK cells, CD8⁺ T cells, and TCR 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-.

Editor: J. B. Bliska

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