PMID- 32279869
OWN - NLM
STAT- MEDLINE
DCOM- 20210902
LR  - 20210902
IS  - 1873-281X (Electronic)
IS  - 1472-9792 (Linking)
VI  - 121
DP  - 2020 Mar
TI  - N6-methylated adenine on the target sites of mamA from Mycobacterium bovis BCG 
      enhances macrophage activation by CpG DNA in mice.
PG  - 101890
LID - S1472-9792(19)30217-3 [pii]
LID - 10.1016/j.tube.2019.101890 [doi]
AB  - CpG motifs in DNA sequences are recognized by Toll-like receptor 9 and activate 
      immune cells. Bacterial genomic DNA (gDNA) has modified cytosine bases 
      (5-methylcytosine [5 mC]) and modified adenine bases (6-methyladenine [6 mA]). 
      5 mC inhibits immune activation by CpG DNA; however, it is unclear whether 6 mA 
      inhibits immune activation by CpG DNA. Mycobacterium bovis BCG (BCG) has three 
      adenine methyltransferases (MTases) that act on specific target sequences. In 
      this study, we examined whether the 6 mA at the target sites of adenine MTases 
      affected the immunostimulatory activity of CpG DNA. Our results showed that only 
      6 mA located at the target sequence of mamA, an adenine MTase from BCG, enhanced 
      interleukin (IL)-12p40 production from murine bone marrow-derived macrophages 
      (BMDMs) stimulated with CpG DNA. Enhancement of IL-12p40 production in BMDMs was 
      also observed when BMDMs were stimulated with CpG DNA ligated to 
      oligodeoxynucleotides (ODNs) harboring 6 mA. Accordingly, we then evaluated 
      whether gDNA from adenine MTase-deficient BCG was less efficient with regard to 
      stimulation of BMDMs. Indeed, gDNA from a mamA-deficient BCG had less ability to 
      activate BMDMs than that from wild-type BCG. We concluded from these results that 
      adenine methylation on ODNs and bacterial gDNA may enhance immune activity 
      induced by CpG DNA.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Tsukamoto, Yumiko
AU  - Tsukamoto Y
AD  - Department of Mycobacteriology, Leprosy Research Center, National Institute of 
      Infectious Diseases, Tokyo, Japan. Electronic address: ytsuka@niid.go.jp.
FAU - Tamura, Toshiki
AU  - Tamura T
AD  - Department of Mycobacteriology, Leprosy Research Center, National Institute of 
      Infectious Diseases, Tokyo, Japan.
FAU - Maeda, Yumi
AU  - Maeda Y
AD  - Department of Mycobacteriology, Leprosy Research Center, National Institute of 
      Infectious Diseases, Tokyo, Japan.
FAU - Miyake, Kensuke
AU  - Miyake K
AD  - Division of Innate Immunity, Department of Microbiology and Immunology, The 
      Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
FAU - Ato, Manabu
AU  - Ato M
AD  - Department of Mycobacteriology, Leprosy Research Center, National Institute of 
      Infectious Diseases, Tokyo, Japan.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191118
PL  - Scotland
TA  - Tuberculosis (Edinb)
JT  - Tuberculosis (Edinburgh, Scotland)
JID - 100971555
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (CPG-oligonucleotide)
RN  - 0 (DNA, Bacterial)
RN  - 0 (Interleukin-12 Subunit p40)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 9)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - JAC85A2161 (Adenine)
RN  - W7IBY2BGAX (6-methyladenine)
SB  - IM
MH  - Adenine/*analogs & derivatives/immunology
MH  - Adjuvants, Immunologic/*pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - DNA, Bacterial/genetics/*immunology
MH  - Host-Pathogen Interactions
MH  - Interleukin-12 Subunit p40/metabolism
MH  - Macrophage Activation/*drug effects
MH  - Macrophages/*drug effects/immunology/metabolism/microbiology
MH  - Methyltransferases/deficiency/genetics/*immunology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mycobacterium bovis/enzymology/genetics/*immunology
MH  - Oligodeoxyribonucleotides/*pharmacology
MH  - Signal Transduction
MH  - Toll-Like Receptor 9/*agonists/genetics/metabolism
EDAT- 2020/04/14 06:00
MHDA- 2021/09/03 06:00
CRDT- 2020/04/14 06:00
PHST- 2019/05/28 00:00 [received]
PHST- 2019/11/11 00:00 [revised]
PHST- 2019/11/15 00:00 [accepted]
PHST- 2020/04/14 06:00 [entrez]
PHST- 2020/04/14 06:00 [pubmed]
PHST- 2021/09/03 06:00 [medline]
AID - S1472-9792(19)30217-3 [pii]
AID - 10.1016/j.tube.2019.101890 [doi]
PST - ppublish
SO  - Tuberculosis (Edinb). 2020 Mar;121:101890. doi: 10.1016/j.tube.2019.101890. Epub 
      2019 Nov 18.