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Infection and Immunity, December 2003, p. 7014-7022, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.7014-7022.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Orally Administered CpG Oligodeoxynucleotide Induces Production of CXC and CC Chemokines in the Gastric Mucosa and Suppresses Bacterial Colonization in a Mouse Model of Helicobacter pylori Infection

S. Raghavan, J. Nyström, M. Fredriksson, J. Holmgren, and A. M. Harandi*

Department of Medical Microbiology and Immunology and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, S 41346 Göteborg, Sweden

Received 14 April 2003/ Returned for modification 1 July 2003/ Accepted 3 September 2003

Bacterial DNA and unmethylated CpG oligodeoxynucleotides (CpG ODN) are known to be potent stimulators of the innate immune system in vitro and in vivo. We therefore investigated if oral administration of CpG ODN could enhance innate immunity in the gastric mucosa and control the extent of Helicobacter pylori infection in mice. Intragastric administration of a single dose of CpG ODN significantly increased local production of the CC chemokines macrophage inflammatory protein 1{alpha} (MIP-1{alpha}), MIP-1ß, and RANTES and the CXC chemokine gamma interferon-inducible protein 10 in the stomach and/or the small intestine. Importantly, intragastric administration of CpG ODN to mice with an already established H. pylori infection, in the absence of any coadministered antigen, was found to reduce the bacterial load in the stomach compared to the load in H. pylori-infected control mice, while similar administration of non-CpG ODN had no effect on the bacterial load. The reduction in the bacterial numbers in the stomachs of mice treated with CpG ODN was associated with enhanced infiltration of immune cells and increased RANTES production in the gastric mucosa compared to the infiltration of immune cells and RANTES production in H. pylori-infected control animals. These findings suggest that intragastric administration of CpG ODN without antigen codelivery may represent a valuable strategy for induction of innate immunity against H. pylori infection.

* Corresponding author. Mailing address: Göteborg University Vaccine Research Institute (GUVAX), Department of Medical Microbiology and Immunology, Medicinaregatan 7A, S40530 Göteborg, Sweden. Phone: 46 31 773 6229. Fax: 46 31 773 6210. E-mail: ali.harandi{at}microbio.gu.se.

Editor: J. T. Barbieri

Infection and Immunity, December 2003, p. 7014-7022, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.7014-7022.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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