CpG oligodeoxynucleotides enhance neonatal resistance to Listeria infection

被引:51
作者
Ito, S
Ishii, KI
Gursel, M
Shirotra, H
Ihata, A
Klinman, DM
机构
[1] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA
[2] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka, Japan
关键词
D O I
10.4049/jimmunol.174.2.777
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Infection by Listeria monocytogenes causes serious morbidity and mortality during the neonatal period. Previous studies established that immuhostimulatory 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 to 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 susceptibillity to infectious pathogens.
引用
收藏
页码:777 / 782
页数:6
相关论文
共 45 条
[1]   Toll-like receptors: critical proteins linking innate and acquired immunity [J].
Akira, S ;
Takeda, K ;
Kaisho, T .
NATURE IMMUNOLOGY, 2001, 2 (08) :675-680
[2]   Emerging foodborne diseases [J].
Altekruse, SF ;
Cohen, ML ;
Swerdlow, DL .
EMERGING INFECTIOUS DISEASES, 1997, 3 (03) :285-293
[3]  
Ballas ZK, 1996, J IMMUNOL, V157, P1840
[4]  
BANCROFT GJ, 1989, J IMMUNOL, V143, P127
[5]  
BANCROFT GJ, 1987, J IMMUNOL, V139, P1104
[6]   NITRIC-OXIDE PRODUCED DURING MURINE LISTERIOSIS IS PROTECTIVE [J].
BOOCKVAR, KS ;
GRANGER, DL ;
POSTON, RM ;
MAYBODI, M ;
WASHINGTON, MK ;
HIBBS, JB ;
KURLANDER, RL .
INFECTION AND IMMUNITY, 1994, 62 (03) :1089-1100
[7]   Neonatal hypersusceptibility to endotoxin correlates with increased tumor necrosis factor production in mice [J].
Cusumano, V ;
Mancuso, G ;
Genovese, F ;
Cuzzola, M ;
Carbone, M ;
Cook, JA ;
Cochran, JB ;
Teti, G .
JOURNAL OF INFECTIOUS DISEASES, 1997, 176 (01) :168-176
[8]  
Elkins KL, 1999, J IMMUNOL, V162, P2291
[9]   Interleukin-12-and gamma interferon-dependent protection against malaria conferred by CpG oligodeoxynucleotide in mice [J].
Gramzinski, RA ;
Doolan, DL ;
Sedegah, M ;
Davis, HL ;
Krieg, AM ;
Hoffman, SL .
INFECTION AND IMMUNITY, 2001, 69 (03) :1643-1649
[10]   Bacterial DNA induces murine interferon-gamma production by stimulation of interleukin-12 and tumor necrosis factor-alpha [J].
Halpern, MD ;
Kurlander, RJ ;
Pisetsky, DS .
CELLULAR IMMUNOLOGY, 1996, 167 (01) :72-78