IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms6853.html
   My bibliography  Save this article

DNase II-dependent DNA digestion is required for DNA sensing by TLR9

Author

Listed:
  • Mei Po Chan

    (The Institute of Medical Science, The University of Tokyo)

  • Masahiro Onji

    (Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences)

  • Ryutaro Fukui

    (The Institute of Medical Science, The University of Tokyo)

  • Kohki Kawane

    (Faculty of Life Sciences, Kyoto Sangyo University)

  • Takuma Shibata

    (The Institute of Medical Science, The University of Tokyo
    CREST, JST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012)

  • Shin-ichiroh Saitoh

    (The Institute of Medical Science, The University of Tokyo)

  • Umeharu Ohto

    (Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku)

  • Toshiyuki Shimizu

    (CREST, JST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku)

  • Glen N. Barber

    (University of Miami Miller School of Medicine)

  • Kensuke Miyake

    (The Institute of Medical Science, The University of Tokyo
    Laboratory of Innate Immunity, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo)

Abstract

DNase II digests DNA in endolysosomes. In the absence of DNase II, undigested DNA activates cytoplasmic DNA-sensing pathways. Little is known, however, about the role of DNase II in endolysosomal DNA sensing by TLR9. Here we show that DNase II is required for TLR9. We test two types of TLR9 ligands, CpG-A and CpG-B, and show that only CpG-A response is impaired in DNase II-deficient dendritic cells (DCs). Enzymatically inactive DNase II mutants cannot rescue CpG-A responses. DNase II cleaves CpG-A from 20-mer to 11-12-mer. The 3′11-mer CpG-A fragment activates DNase II-deficient DCs. CpG-A shows higher co-localization with LAMP-2+ lysosomes than CpG-B and induces DNase II localization in LAMP-2+ lysosomes. Moreover, we demonstrate that DNase II is required for TLR9 activation by bacterial genomic DNA. Taken together, these results demonstrate that TLR9 responds to DNA fragments generated by DNase II.

Suggested Citation

  • Mei Po Chan & Masahiro Onji & Ryutaro Fukui & Kohki Kawane & Takuma Shibata & Shin-ichiroh Saitoh & Umeharu Ohto & Toshiyuki Shimizu & Glen N. Barber & Kensuke Miyake, 2015. "DNase II-dependent DNA digestion is required for DNA sensing by TLR9," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6853
    DOI: 10.1038/ncomms6853
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6853
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6853?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6853. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.