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Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against Burkholderia pseudomallei Infection in BALB/c Mice

Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against... Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against Burkholderia pseudomallei Infection in BALB/c Mice Apichaya Puangpetch a , c , Robert Anderson d , Yan Y. Huang d , Rasana W. Sermswan b , c , Wanpen Chaicumpa e , Stitaya Sirisinha f and Surasakdi Wongratanacheewin a , c a Department of Microbiology b Department of Biochemistry c Melioidosis Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand d Departments of Microbiology & Immunology and Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada e Department of Parasitology, Faculty of Medicine, Siriraj Hospital f Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand ABSTRACT Melioidosis is a severe disease caused by the Gram-negative bacterium Burkholderia pseudomallei . Previously we showed that pretreatment of mice with CpG oligodeoxynucleotide (CpG ODN) 2 to 10 days prior to B. pseudomallei challenge conferred as high as 90% protection, but this window of protection was rather short. In the present study, we therefore aimed to prolong this protective window and to gain further insight into the mechanisms underlying the protection induced by CpG ODN against B. pseudomallei infection. It was found that the CpG ODN incorporated with cationic liposomes (DOTAP) but not zwitterionic liposomes (DOPC) provided complete protection against bacterial challenge. Although marked elevation of gamma interferon (IFN-γ) was found in the infected animals 2 days postinfection, it was significantly lowered by the DOTAP-plus-CpG ODN pretreatment. When appropriately activated, the phagocytic index and oxidative burst responses of neutrophils appeared not to be elevated. However, macrophages from stimulated mice showed higher levels of nitric oxide production and exhibited higher levels of antimicrobial activities, judging from lower numbers of viable intracellular bacteria. Taken together, our results demonstrate that DOTAP can enhance the protective window period of CpG ODN to at least 30 days and provide 100% protection against B. pseudomallei infection. The protective effect of DOTAP plus CpG ODN could provide an alternative approach to preventing this lethal infection, for which no vaccine is yet available. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical and Vaccine Immunology American Society For Microbiology

Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against Burkholderia pseudomallei Infection in BALB/c Mice

Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against Burkholderia pseudomallei Infection in BALB/c Mice

Clinical and Vaccine Immunology , Volume 19 (5): 675 – May 1, 2012

Abstract

Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against Burkholderia pseudomallei Infection in BALB/c Mice Apichaya Puangpetch a , c , Robert Anderson d , Yan Y. Huang d , Rasana W. Sermswan b , c , Wanpen Chaicumpa e , Stitaya Sirisinha f and Surasakdi Wongratanacheewin a , c a Department of Microbiology b Department of Biochemistry c Melioidosis Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand d Departments of Microbiology & Immunology and Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada e Department of Parasitology, Faculty of Medicine, Siriraj Hospital f Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand ABSTRACT Melioidosis is a severe disease caused by the Gram-negative bacterium Burkholderia pseudomallei . Previously we showed that pretreatment of mice with CpG oligodeoxynucleotide (CpG ODN) 2 to 10 days prior to B. pseudomallei challenge conferred as high as 90% protection, but this window of protection was rather short. In the present study, we therefore aimed to prolong this protective window and to gain further insight into the mechanisms underlying the protection induced by CpG ODN against B. pseudomallei infection. It was found that the CpG ODN incorporated with cationic liposomes (DOTAP) but not zwitterionic liposomes (DOPC) provided complete protection against bacterial challenge. Although marked elevation of gamma interferon (IFN-γ) was found in the infected animals 2 days postinfection, it was significantly lowered by the DOTAP-plus-CpG ODN pretreatment. When appropriately activated, the phagocytic index and oxidative burst responses of neutrophils appeared not to be elevated. However, macrophages from stimulated mice showed higher levels of nitric oxide production and exhibited higher levels of antimicrobial activities, judging from lower numbers of viable intracellular bacteria. Taken together, our results demonstrate that DOTAP can enhance the protective window period of CpG ODN to at least 30 days and provide 100% protection against B. pseudomallei infection. The protective effect of DOTAP plus CpG ODN could provide an alternative approach to preventing this lethal infection, for which no vaccine is yet available.

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Publisher
American Society For Microbiology
Copyright
Copyright © 2012 by the American society for Microbiology.
ISSN
1556-6811
eISSN
1556-679X
DOI
10.1128/CVI.05545-11
pmid
22441390
Publisher site
See Article on Publisher Site

Abstract

Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against Burkholderia pseudomallei Infection in BALB/c Mice Apichaya Puangpetch a , c , Robert Anderson d , Yan Y. Huang d , Rasana W. Sermswan b , c , Wanpen Chaicumpa e , Stitaya Sirisinha f and Surasakdi Wongratanacheewin a , c a Department of Microbiology b Department of Biochemistry c Melioidosis Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand d Departments of Microbiology & Immunology and Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada e Department of Parasitology, Faculty of Medicine, Siriraj Hospital f Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand ABSTRACT Melioidosis is a severe disease caused by the Gram-negative bacterium Burkholderia pseudomallei . Previously we showed that pretreatment of mice with CpG oligodeoxynucleotide (CpG ODN) 2 to 10 days prior to B. pseudomallei challenge conferred as high as 90% protection, but this window of protection was rather short. In the present study, we therefore aimed to prolong this protective window and to gain further insight into the mechanisms underlying the protection induced by CpG ODN against B. pseudomallei infection. It was found that the CpG ODN incorporated with cationic liposomes (DOTAP) but not zwitterionic liposomes (DOPC) provided complete protection against bacterial challenge. Although marked elevation of gamma interferon (IFN-γ) was found in the infected animals 2 days postinfection, it was significantly lowered by the DOTAP-plus-CpG ODN pretreatment. When appropriately activated, the phagocytic index and oxidative burst responses of neutrophils appeared not to be elevated. However, macrophages from stimulated mice showed higher levels of nitric oxide production and exhibited higher levels of antimicrobial activities, judging from lower numbers of viable intracellular bacteria. Taken together, our results demonstrate that DOTAP can enhance the protective window period of CpG ODN to at least 30 days and provide 100% protection against B. pseudomallei infection. The protective effect of DOTAP plus CpG ODN could provide an alternative approach to preventing this lethal infection, for which no vaccine is yet available.

Journal

Clinical and Vaccine ImmunologyAmerican Society For Microbiology

Published: May 1, 2012

References