DNA degradation products attenuate immune response

Researchers of the Department of Synthetic Biology and Immunology from National Institute of Chemistry revealed that very short fragments of DNA amplify immune response to bacterial and viral DNA.

Bacterial and viral infections trigger activation of innate immune response and condition the body to fight infections. Furthermore, the immune system provides assistance in repairing tissue damage and clearance of cancer cells. Microbial infections are among other receptors detected by membrane receptors and endosomal membrane Toll like receptor 9 detects single stranded fragments DNA of bacteria and viruses.
Already decade ago scientists determined that bacterial and viral DNA binds to receptors of innate immunity and activates immune response to infection. They showed, on the other side, that activation of these receptors closely associates with autoimmune diseases. Recently, Japanese scientists determined the crystal structure of single-stranded DNA and Toll-like receptor 9 complex, which has failed to explain how TLR9 recognizes the DNA degradation products.
Researchers of from National Institute of Chemistry showed that in addition to the longer agonistic DNA fragments, the very short fragments of DNA bind to receptor and significantly attenuate immune response. This discovery is important in the design of new receptor agonists for vaccine adjuvants and cancer immunotherapy. At the same time the discovery indicates that proven presence of very short DNA fragments can influence the development and maintenance of inflammation of autoimmune diseases.

Figure (a) shows binding of short DNA fragments to a receptor TLR9 together with longer fragments of single-stranded DNA that activate immune response. (b, c, d) Amplification of immune response to longer single-stranded DNA and bacterial DNA by short DNA fragments is shown. (e) The short DNA fragments and longer single-stranded DNA colocalize in the early and late endosomes, where both forms of DNA interact with the receptor TLR9 and activate the immune response.

The results have been published in Nature Communications.

The researchers: Jelka Pohar, Karolina Ivičak Kocjan, Duško Lainšček, Miša-Mojca Cajnko Roman Jerala and Mojca Benčina.
Title: Short single stranded DNA degradation products augment the activation of Toll-like receptor 9

The mentioned publication completes the research on the mechanisms of activation of the innate immune response to bacterial and viral infections. Research has been fully designed and implemented at the National Institute of Chemistry, using the equipment of ENFIST Center of Excellence and funded by the ARRS agency.

Related publications:

  • POHAR, Jelka, YAMAMOTO, Chikako, FUKUI, Ryutaro, CAJNKO, Miša Mojca, MIYAKE, Kensuke, JERALA, Roman, BENČINA, Mojca (2017) Selectivity of human TLR9 for double CpG motifs and implications for the recognition of genomic DNA. J Immunol 198, 2093-2104.
  • POHAR, Jelka, KUŽNIK, Alenka, JERALA, Roman, BENČINA, Mojca (2015) Minimal sequence requirements for oligodeoxyribonucleotides activating human TLR9. J Immunol 194, 3901-3908.
  • POHAR, Jelka, LAINŠČEK, Duško, FUKUI, Ryutaro, YAMAMOTO, Chikako, MIYAKE, Kensuke, JERALA, Roman, BENČINA, Mojca (2015) Species-specific minimal sequence motif for oligodeoxyribonucleotides activating mouse TLR9. The journal of immunology 195, 4396-4405.
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