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

Nature Communications
Jelka PoharMojca Benčina

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.

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Citations

Jul 3, 2018·FEBS Letters·Hanako IshidaToshiyuki Shimizu
Sep 29, 2018·Annual Review of Virology·Zhe MaBlossom Damania
Jun 20, 2018·Journal of Leukocyte Biology·Karolina Ivičak-KocjanMojca Benčina
Nov 1, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elena Montes-CobosFriederike Ufer
Mar 14, 2020·Cell·Katherine A Fitzgerald, Jonathan C Kagan
Aug 29, 2020·Biomacromolecules·Anh Thi Tram TuTomohiko Yamazaki

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Datasets Mentioned

BETA
ABIN2486165

Methods Mentioned

BETA
PCR
immunoprecipitation
flow cytometry
transfection
Assay
electrophoresis
ELISA
lavages
FACS

Software Mentioned

ImageJ
Origin
LAS AF
GraphPad Prism

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