An immunostimulatory oligodeoxynucleotide containing a cytidine-guanosine motif protects senescence-accelerated mice from lethal influenza virus by augmenting the T helper type 1 response.
The SAM-P1 strain of senescence-accelerated model mice shows an impaired T helper type 1 (Th1) immune response upon infection with influenza virus, which results in high susceptibility to the virus. Treatment of spleen cells from SAM-P1 mice with an immunostimulatory oligodeoxynucleotide containing a cytidine-guanosine motif (CpG ODN) in vitro increased the ratio of the titre of IFN-gamma to that of IL-4. Administration of CpG ODN to SAM-P1 mice generated satisfactory virus-specific cytotoxic T-lymphocyte responses and natural killer cell activation and the virus-specific immunoglobulin (Ig) isotype switched from IgG1 to IgG2a. Virus growth in the lungs of CpG ODN-treated SAM-P1 mice was cleared quickly and mice survived the lethal influenza virus infection. It could be inferred that a possible mechanism of CpG ODN for normalization of senescence-associated dysregulation of the Th1/Th2 balance involves the upregulated expression of CD154 and CD40 molecules on immune-competent cells. These results suggest that CpG ODN could contribute to the development of a protective strategy against infectious diseases, especially among immunocompromised elderly persons, by stimulating Th1 immune responses.
Dong
Li
L
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaizuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Mori
Isamu
I
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaizuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Hossain
Md Jaber
MJ
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaizuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Liu
Beixing
B
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaizuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Kimura
Yoshinobu
Y
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaizuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D019588:Aging, Premature / Q000188:drug therapy* / Q000276:immunology*; D000818:Animals; D001483:Base Sequence; D023201:CD40 Ligand / Q000378:metabolism; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma