基因组DNA
免疫系统
CpG站点
DNA
DNA甲基化
生物
分子生物学
DNA甲基转移酶
CpG寡核苷酸
甲基转移酶
甲基化
化学
细胞生物学
基因
遗传学
基因表达
作者
Yumiko Tsukamoto,Toshiki Tamura,Yumi Maeda,Kensuke Miyake,Manabu Ato
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2020-05-01
卷期号:204 (1_Supplement): 226.17-226.17
标识
DOI:10.4049/jimmunol.204.supp.226.17
摘要
Abstract Background and Aim CpG motifs in DNA sequences are recognized by TLR9 and activate immune cells. Bacterial genomic DNA (gDNA) has modified cytosine bases (5-methylcytosine (5mC)) and modified adenine bases (6-methyladenine (6mA)). It is well-known that 5mC inhibits immune activation by CpG DNA; however, it is still unclear whether 6mA inhibits immune activation by CpG DNA. In this study, we tried to examine whether the existence of 6mA affected the immunostimulatory activity of gDNA. Materials and Methods We focused on adenine methyltransferases (MTases) expressed by Mycobacterium bovis BCG (BCG). Each adenine MTases has specific target sites. Therefore, we used oligodeoxynucleotides (ODNs) with 6mA on the target sequences of MTases from BCG. We stimulated murine bone-marrow derived macrophages (BMDMs) with ODNs harboring 6mA or ODNs without 6mA. We then compared the immunostimulatory activity of ODNs with 6mA to ODNs without 6mA using. We also developed adenine MTase-deficient BCG. We analyzed whether 6mA on gDNA from BCG is involved in the immunostimulatory activity of BCG gDNA. Results Our results showed that 6mA located at the target sequence of mamA, an adenine MTase from BCG, enhanced IL-12p40 production from BMDMs stimulated with CpG DNA. We also observed that gDNA from mamA-deficient BCG induced less IL-12p40 from BMDMs than gDNA from mamA-intact BCG. Conclusion We concluded from these results that adenine methylation on ODNs may enhance immune activity induced by bacterial gDNA.
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