Strong immunostimulation in murine immune cells by Lactobacillus rhamnosus GG DNA containing novel oligodeoxynucleotide pattern.
Whole cells, cell wall components and some soluble factors from Lactobacillus rhamnosus GG (LGG) are known to invoke immune responses as they interact with animal and human immune cells. In the present study, we found that chromosomal DNA from LGG is a potent inducer of splenic B cell proliferation, CD86/CD69 expression and cytokine production in mice. In the genomic DNA of LGG we discovered TTTCGTTT oligodeoxynucleotide (ODN) ID35, which has a potent activity in a number of immunostimulatory assays. Phosphorothioate backbone is not required for the activity of ID35. The ODN ID35 showed levels of activity comparable with those induced by the murine prototype ODN 1826 in B cell proliferation, CD86/CD69 expression, interleukin (IL)-6, IL-12, IL-18, interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) mRNA expression and IFN-gamma/IL-12p70 protein production assays. Additionally, ID35 appeared to be equally active in both murine and human immune cells. These stimulatory effects are due to TTTCGTTT motif located in the 5' end of ID35. In this study we demonstrate for a first time that, DNA from LGG is a factor of immunobiotic activity. Furthermore, ODN ID35 is the first ODN, with such a strong immunostimulatory activity to be found in immunobiotic bacterial DNA.
Iliev
Iliyan D
ID
Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
Kitazawa
Haruki
H
Shimosato
Takeshi
T
Katoh
Shinichiro
S
Morita
Hirotsugu
H
He
Fang
F
Hosoda
Masataka
M
Saito
Tadao
T
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051940:B7-2 Antigen; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002876:Chromosomes, Bacterial / Q000235:genetics; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007778:Lactobacillus / Q000235:genetics*; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D014158:Transcription, Genetic; D000099192:CD69 Antigens
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051940:B7-2 Antigen; D016207:Cytokines; D004269:DNA, Bacterial; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D009841:Oligonucleotides; D000099192:CD69 Antigens; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; C503529:ODN ID35