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Short single-stranded DNA degradation products augment the activation of Toll-like receptor 9

Author

Listed:
  • Jelka Pohar

    (National Institute of Chemistry)

  • Duško Lainšček

    (National Institute of Chemistry)

  • Karolina Ivičak-Kocjan

    (National Institute of Chemistry)

  • Miša-Mojca Cajnko

    (National Institute of Chemistry)

  • Roman Jerala

    (National Institute of Chemistry
    EN-FIST Centre of Excellence)

  • Mojca Benčina

    (National Institute of Chemistry
    EN-FIST Centre of Excellence)

Abstract

Toll-like receptors encounter a diversity of degradation products in endosomes. TLR7 and TLR8 have been shown to be activated by RNA degradation products. Here we show that although TLR9 requires single-stranded DNA longer than 20 nucleotides for a robust response, TLR9 activation is augmented by CpG-containing oligodeoxyribonucleotides (sODNs) as short as 2 nucleotides, which, by themselves, do not induce activation in cell cultures, as well as in mice. sODNs also activate human TLR9 in combination with ODNs containing a single CpG motif that by themselves do not activate human TLR9. The specific sequence motif of sODN and colocalization of ODN and sODN suggest that the mechanism of activation involves binding of both ODN and sODN to TLR9. sODNs augment TLR9 activation by mammalian genomic DNA indicating the role of short DNA degradation products in the endosomes in response to infection or in autoimmune disease, particularly at limiting concentrations of ODNs.

Suggested Citation

  • Jelka Pohar & Duško Lainšček & Karolina Ivičak-Kocjan & Miša-Mojca Cajnko & Roman Jerala & Mojca Benčina, 2017. "Short single-stranded DNA degradation products augment the activation of Toll-like receptor 9," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15363
    DOI: 10.1038/ncomms15363
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    Cited by:

    1. Amanda L. Gavin & Deli Huang & Tanya R. Blane & Therese C. Thinnes & Yusuke Murakami & Ryutaro Fukui & Kensuke Miyake & David Nemazee, 2021. "Cleavage of DNA and RNA by PLD3 and PLD4 limits autoinflammatory triggering by multiple sensors," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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