Identification of a potent immunostimulatory oligodeoxynucleotide from Streptococcus thermophilus lacZ.
Immunostimulatory sequences of oligodeoxynucleotides (ODNs), such as CpG ODNs, are potent stimulators of innate immunity. Here, we identified a strong immunostimulatory CpG ODN, which we named MsST, from the lac Z gene of Streptococcus (S.) thermophilus ATCC19258, and we evaluated its immune functions. In in vitro studies, MsST had a similar ability as the murine prototype CpG ODN 1555 to induce inflammatory cytokine production and cell proliferation. In mouse splenocytes, MsST increased the number of CD80+CD11c+and CD86+CD11c+ dendritic cells and CD4+CD25+ regulatory T cells. We also analyzed the effects of MsST on the expression of regulatory cytokines by real-time quantitative PCR. MsST was more potent at inducing interleukin-10 expression than the ODN control 1612, indicating that MsST can augment the regulatory T cell response via Toll-like receptor 9, which plays an important role in suppressing T helper type 2 responses. These results suggest that S. thermophilus, whose genes include a strong Immunostimulatory sequence-ODN, is a good candidate for a starter culture to develop new physiologically functional foods and feeds.
Shimosato
Takeshi
T
Fiber-Nanotech Young Researcher Empowerment Center, Shinshu University, Minamiminowa, Kamiina, Japan. shimot@shinshu-u.ac.jp
Tohno
Masanori
M
Sato
Takashi
T
Nishimura
Junko
J
Kawai
Yasushi
Y
Saito
Tadao
T
Kitazawa
Haruki
H
D000821:Animal Feed / Q000382:microbiology; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D055951:Functional Food / Q000382:microbiology; D007249:Inflammation / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048249:Streptococcus thermophilus / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001616:beta-Galactosidase / Q000235:genetics
D015703:Antigens, CD; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D016753:Interleukin-10; D001616:beta-Galactosidase