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The Journal of Immunology, 1999, 162: 2291-2298.
Copyright © 1999 by The American Association of Immunologists

Bacterial DNA Containing CpG Motifs Stimulates Lymphocyte-Dependent Protection of Mice Against Lethal Infection with Intracellular Bacteria1

Karen L. Elkins2,*, Tonya R. Rhinehart-Jones*, Scott Stibitz{dagger}, Jacqueline S. Conover{ddagger} and Dennis M. Klinman{ddagger}

* Laboratory of Mycobacteria, Division of Bacterial Products, {dagger} Laboratory of Enteric and Sexually Transmitted Diseases, Division of Bacterial Products, and {ddagger} Retroviral Immunology Section, Laboratory of Retrovirology, Division of Viral Products, Center for Biologics Evaluation and Research, Rockville, MD 20852

Bacterial DNA containing unmethylated CpG motifs activates mammalian lymphocytes and macrophages to produce cytokines and polyclonal Ig. These include IFN-{gamma}, IL-12, TNF-{alpha}, and IL-6, which are important in the control of intracellular bacterial infection. Here, we show that bacterial DNA, as well as synthetic oligonucleotides containing CpG motifs, induce protection against large lethal doses of Francisella tularensis live vaccine strain (LVS) and Listeria monocytogenes. Methylation of DNA at CpG dinucleotides or inversion of the motif abolished this protection. Surprisingly, DNA-mediated protection was highly dependent on lymphocytes, particularly B cells, as well as the production of IFN-{gamma}. Optimal protection was elicited 2–3 days after inoculation with DNA and persisted for up to 2 wk. Further, animals surviving lethal challenge developed pathogen-specific secondary immunity. These findings indicate that host innate immune responses to bacterial DNA may contribute to the induction of protective immunity to bacteria and the subsequent development of memory.




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