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Infection and Immunity, August 2003, p. 4398-4404, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4398-4404.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Oral Pretreatment of Mice with CpG DNA Reduces Susceptibility to Oral or Intraperitoneal Challenge with Virulent Listeria monocytogenes

Nancy B. Ray1* and Arthur M. Krieg1,2

Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242,1 Coley Pharmaceutical Group, Wellesley, Massachusetts 024812

Received 9 December 2002/ Returned for modification 19 February 2003/ Accepted 13 May 2003

Listeria monocytogenes is an enteroinvasive intracellular bacterial pathogen that infects humans and other animals, including mice, sometimes resulting in severe systemic infections. Previous studies showed that intraperitoneal (i.p.) pretreatment of susceptible BALB/c mice with immune-stimulatory CpG DNA 48 to 96 h prior to i.p. challenge with virulent L. monocytogenes reduces bacterial numbers in livers by greater than 100-fold, correlating with recovery from infection. Here we show that oral pretreatment of BALB/c mice with CpG DNA results in decreased susceptibility to either oral or i.p. challenge with L. monocytogenes. A single dose of 200 µg of CpG DNA administered to BALB/c mice orally by gavage 48 h or 7 days before oral challenge with virulent L. monocytogenes reduces bacterial numbers approximately 10- to 100-fold in livers and spleens. Lymphotoxin alpha knockout mice lacking Peyer's patches (PPs) and pretreated orally with CpG DNA 48 h prior to oral challenge with L. monocytogenes also have reduced susceptibility to infection, suggesting that PPs are required neither for oral infection nor for CpG-induced resistance against oral infection with L. monocytogenes. Surprisingly, 48-h oral pretreatment of BALB/c mice with 100 to 200 µg of CpG DNA results in approximately 100-fold-decreased bacterial numbers in livers following i.p. challenge with L. monocytogenes, suggesting, along with other data in this report, that orally delivered CpG DNA induces systemic resistance to infection. These results indicate that oral administration of CpG DNA induces systemic innate immune defenses against either oral or systemic infection with virulent L. monocytogenes.

* Corresponding author. Mailing address: Department of Pathology, 10E14A/VA, University of Iowa, Iowa City, IA 52242. Phone: (319) 338-0581, ext. 7542. Fax: (319) 339-7148. Email: nancy-ray{at}uiowa.edu.

Editor: B. B. Finlay

Infection and Immunity, August 2003, p. 4398-4404, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4398-4404.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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