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Infection and Immunity, April 2009, p. 1589-1595, Vol. 77, No. 4
0019-9567/09/$08.00+0 doi:10.1128/IAI.01257-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Caspase-1 Mediates Resistance in Murine Melioidosis
Katrin Breitbach,1
Guang Wen Sun,2
Jens Köhler,1
Kristin Eske,1
Patimaporn Wongprompitak,1,3
Gladys Tan,4
Yichun Liu,4
Yunn-Hwen Gan,2 and
Ivo Steinmetz1*
Friedrich Loeffler Institute of Medical Microbiology, Ernst Moritz Arndt University Greifswald, Greifswald, Germany,1 Department of Biochemistry, National University of Singapore, Singapore, Republic of Singapore,2 Department of Immunology, Faculty of Medicine Siriraj, Mahidol University, Bangkok, Thailand,3 Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore, Republic of Singapore4
Received 14 October 2008/ Returned for modification 19 December 2008/ Accepted 18 January 2009
The gram-negative rod Burkholderia pseudomallei is the causative agent of melioidosis, a potentially fatal disease which is endemic in tropical and subtropical areas. The bacterium multiplies intracellularly within the cytosol, induces the formation of actin tails, and can spread directly from cell to cell. Recently, it has been shown that B. pseudomallei can induce caspase-1-dependent cell death in macrophages. The aim of the present study was to further elucidate the role of caspase-1 during B. pseudomallei infection. In vivo experiments with caspase-1–/– mice revealed a high susceptibility to B. pseudomallei challenge. This phenotype was associated with a significantly higher bacterial burden 2 days after infection and decreased gamma interferon (IFN-
) and interleukin-18 cytokine levels 24 h after infection compared to control animals. caspase-1–/– bone marrow-derived macrophages (BMM) exhibited strong caspase-3 expression and reduced cell damage compared to wild-type (WT) cells during early B. pseudomallei infection, indicating "classical" apoptosis, whereas WT BMM showed signs of rapid caspase-1-dependent cell death. Moreover, we found that caspase-1–/– BMM had a strongly increased bacterial burden compared to WT cells 3 h after infection under conditions where no difference in cell death could be observed between both cell populations at this time point. We therefore suggest that caspase-1-dependent rapid cell death might contribute to resistance by reducing the intracellular niche for B. pseudomallei, but, in addition, caspase-1 might also have a role in controlling intracellular replication of B. pseudomallei in macrophages. Moreover, caspase-1-dependent IFN- production is likely to contribute to resistance in murine melioidosis.
* Corresponding author. Mailing address: Friedrich Loeffler Institute of Medical Microbiology, Ernst Moritz Arndt University Greifswald, Martin Luther Str. 6, 17489 Greifswald, Germany. Phone: 49 (0) 3834 865587. Fax: 49 (0) 3834 865561. E-mail: steinmetz.ivo{at}uni-greifswald.de
Published ahead of print on 29 January 2009.
Infection and Immunity, April 2009, p. 1589-1595, Vol. 77, No. 4
0019-9567/09/$08.00+0 doi:10.1128/IAI.01257-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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