Ito Shuichi, Ishii Ken J, Gursel Mayda, Shirotra Hidekazu, Ihata Atsushi, Klinman Dennis M
Section of Retroviral Immunology, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
J Immunol. 2005 Jan 15;174(2):777-82. doi: 10.4049/jimmunol.174.2.777.
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-gamma, IL-12, and/or TNF-alpha. 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.
单核细胞增生李斯特菌感染在新生儿期可导致严重的发病和死亡。先前的研究表明,免疫刺激的CpG寡脱氧核苷酸(ODN)可增强成年小鼠对包括李斯特菌在内的多种传染性病原体的抵抗力。这项工作研究了CpG ODN刺激新生儿产生保护性免疫反应的能力。结果表明,3日龄小鼠的树突状细胞、巨噬细胞和B细胞通过分泌γ干扰素、白细胞介素-12和/或肿瘤坏死因子-α对CpG刺激作出反应。经CpG处理的新生儿的脾细胞在体外接触细菌时会产生大量细胞因子和一氧化氮。用CpG ODN处理的新生儿可免受致命的李斯特菌攻击,并产生抗原特异性的CD4和CD8 T细胞,从而提供针对后续感染的长期保护。这些结果表明,新生儿免疫系统的细胞成分对CpG ODN的刺激有反应,从而降低宿主对传染性病原体的易感性。