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Infection and Immunity, August 2004, p. 4494-4502, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4494-4502.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Immunostimulatory CpG Oligodeoxynucleotide Confers Protection in a Murine Model of Infection with Burkholderia pseudomallei

Surasakdi Wongratanacheewin,1* Wannapa Kespichayawattana,2 Pakamas Intachote,2 Sathit Pichyangkul,3 Rasana W. Sermswan,4 Arthur M. Krieg,5 and Stitaya Sirisinha6

Department of Microbiology,1 Department of Biochemistry,4 Faculty of Medicine, Khon Kaen University, Khon Kaen, Laboratory of Immunology, Chulabhorn Research Institute,2 Department of Immunology and Medicine, U.S. Army Medical Component, AFRIMS,3 Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand,6 Coley Pharmaceutical Group, Wellesley, Massachusetts5

Received 15 February 2004/ Returned for modification 2 March 2004/ Accepted 10 May 2004

Although CpG oligodeoxynucleotides (CpG ODNs) are known to enhance resistance against infection in a number of animal models, little is known about the CpG-induced protection against acute fatal sepsis such as that associated with the highly virulent bacterium Burkholderia pseudomallei. We previously demonstrated in an in vitro study that immunostimulatory CpG ODN 1826 enhances phagocytosis of B. pseudomallei and induces nitric oxide synthase and nitric oxide production by mouse macrophages. In the present study, CpG ODN 1826 given intramuscularly to BALB/c mice 2 to 10 days prior to B. pseudomallei challenge conferred better than 90% protection. CpG ODN 1826 given 2 days before the bacterial challenge rapidly enhanced the innate immunity of these animals, judging from the elevated serum levels of interleukin-12 (IL-12)p70 and gamma interferon (IFN-{gamma}) over the baseline values. No bacteremia was detected on day 2 in 85 to 90% of the CpG-treated animals, whereas more than 80% of the untreated animals exhibited heavy bacterial loads. Although marked elevation of IFN-{gamma} was found consistently in the infected animals 2 days after the bacterial challenge, it was ameliorated by the CpG ODN 1826 pretreatment (P = 0.0002). Taken together, the kinetics of bacteremia and cytokine profiles presented are compatible with the possibility that protection by CpG ODN 1826 against acute fatal septicemic melioidosis in this animal model is associated with a reduction of bacterial load and interference with the potential detrimental effect of the robust production of proinflammatory cytokines associated with B. pseudomallei multiplication.

* Corresponding author. Mailing address: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Phone: (66-43) 363515. Fax: (66-43) 348385. E-mail, sura_wng{at}kku.ac.th.

Editor: J. D. Clements

Infection and Immunity, August 2004, p. 4494-4502, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4494-4502.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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