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CpG Oligodeoxynucleotides Enhance Neonatal Resistance to Listeria Infection

Shuichi Ito^*, Ken J. Ishii, Mayda Gursel^*, Hidekazu Shirotra^*, Atsushi Ihata^* and Dennis M. Klinman^1,*

^* Section of Retroviral Immunology, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892; and Department of Host Defense, Research Institute for Microbial Diseases. Osaka University, Osaka, Japan

Infection by Listeria monocytogenes causes serious morbidity and mortality during the neonatal period. Previous studies established that immunostimulatory CpG oligodeoxynucleotides (ODN) can increased the resistance of adult mice to many infectious pathogens, including Listeria. This work examines the capacity of CpG ODN to stimulate a protective immune response in newborns. Results indicate that dendritic cells, macrophages, and B cells from 3-day-old mice respond to CpG stimulation by secreting IFN-, IL-12, and/or TNF-. Spleen cells from CpG-treated neonates produce large amounts of cytokine and NO when exposed to bacteria in vitro. Newborns treated with CpG ODN are protected from lethal Listeria challenge and generate Ag-specific CD4 and CD8 T cells that afford long-term protection against subsequent infection. These results demonstrate that cellular elements of the neonatal immune system respond to stimulation by CpG ODN, thereby reducing host susceptibility to infectious pathogens.

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