Search
Submit an article RU
Advanced targets in Biomedicine

Current issue

Back to the list Download the article
ENG
Сохранить XML для: JATS (вып.)
Gavrilova E. D. Goiman E. V. Demchenko E. N. Chub E. V. Volsky N. N. Kozlov V. A.

Modulation of the inflammatory response in experimental models of mice of different strains using synthetic TLR9 ligands

DOI
10.5922/ATB-2026-2-1-6
Pages
89-100
To cite
Gavrilova E. D., Goiman E. V., Demchenko E. N., Chub E. V., Volsky N. N., Kozlov V. A. Modulation of the inflammatory response in experimental models of mice of different strains using synthetic TLR9 ligands. Advanced Targets in Biomedicine. 2026;2(1):89–100. https://doi.org/10.5922/ATB-2026-2-1-6
cell-free DNA TLR9 oligonucleotides inflammation TNF-α LPS

Abstract

Cell-free DNA (cfDNA) from animals and humans possesses immunomodulatory properties, and the underlying me­chanism of its action may involve binding to pattern recognition receptors such as TLR9. Activation of these receptors initiates inflammation and increases the production of proinflammatory cytokines. It is therefore relevant to study the effect of TLR9 receptor activation by the specific agonist ODN 1826 on changes in blood cfDNA levels and TNF-α production in response to an exogenous proinflammatory stimulus in C57BL/6 and Balb/c mice — strains known to differ in their response to the development of inflammation.

It was found that administration of the TLR9 receptor agonist ODN 1826 increased inflammation intensity in LPS-treated mice, as characterized by increased TNF-α and cfDNA concentrations in the blood and a decrease in the content of cfDNA covalently bound to proteins on the cell surface. At the early stage of inflammation development, the response of Balb/c mice to LPS was not qualitatively different from that of C57BL/6 mice.

These results suggest that agents capable of activating TLR9 may prove to be effective pharmacological tools for the treatment of immunopathological processes requiring correction of the Th1/Th2 balance.

Reference

  1. Ferrera F., Altosole T., Tardito S., Astone G., Bernardi C., Parodi A., et al. Immunoregulatory properties of cell free DNA. Cell Mol. Life Sci. 2025, 82(1), 320, DOI: 10.1007/s00018-025-05862-y.
  2. Wang Y., Du C., Zhang Y., Zhu L. Composition and function of neutrophil extracellular Traps. Biomolecules. 2024, 14(4), 416, DOI: 10.3390/biom14040416.
  3. Singhal A., Kumar S. Neutrophil and remnant clearance in immunity and inflammation.// Immunology. 2022, 165, 22—43, DOI: 10.1111/imm.13423.
  4. Műzes G., Bohusné Barta B., Szabó O., Horgas V., Sipos F. Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors. Biomedicines, 2022, 10(11), 2853, DOI: 10.3390/biomedicines10112853.
  5. Zhang Y., Liu Z., Ji K., Li X., Wang C., Ren Z., et al. Clinical Application Value of Circula­ting Cell-free DNA in Hepatocellular Carcinoma. Front. Mol. Biosci. 2021, 8, 736330, DOI: 10.3389/fmolb.2021.736330.
  6. Смирнова С. Ю., Никулина Е. Е., Габеева Н. Г., Королева Д. А., Татарникова С. А., Смольянинова А. К., и др. Свободно циркулирующая ДНК в плазме у пациентов с диффузной В-крупноклеточной лимфомой и В-клеточной лимфомой высокой степени злокачественности (‘double hit’/’triple hit’). Клиническая онкогематология. 2023, 16(2), 200—208, DOI: 10.21320/2500-2139-2023-16-2-200-208.
  7. Киреева В. В., Лепехова С. А., Иноземцев П. О., Усольце Ю. К., Трофимова Е. А. Роль митохондриальной ДНК в патогенезе сердечно-сосудистых заболеваний. Казанский медицинский журнал. 2022, 103(3), 455—466, DOI: 10.17816/KMJ2022-455.
  8. McCarthy C. G., Wenceslau C. F., Goulopoulou S., Ogbi S., Baban B., Sullivan J. C., et al. Circulating mitochondrial DNA and Toll-like receptor 9 are associated with vascular dysfunction in spontaneously hypertensive rats. Cardiovasc. Res., 2015, 107(1), 119—130, DOI: 10.1093/cvr/cvv137.
  9. Brynychova I., Zinkova A., Hoffmanova I., Korabecna M., Dankova P. Immunoregulatory properties of cell-free DNA in plasma of celiac disease patients — A pilot study. Autoimmunity, 2019, 52(2), 88—94, DOI: 10.1080/08916934.2019.1608965.
  10. Saber M. M., Monir N., Awad A. S., Elsherbiny M. E., Zaki H. F. TLR9: A friend or a foe. Life Sci. 2022, 307, 120874, DOI: 10.1016/j.lfs.2022.120874.
  11. Okude H., Ori D., Kawai T. Signaling Through Nucleic Acid Sensors and Their Roles in Inflammatory Diseases. Front. Immunol., 2021, 11, 625833, DOI: 10.3389/fimmu.2020.625833.
  12. Liu H., Ji Y., Ma X., He A., Zhao W., Zhang P., et al. Effects of CpG oligodeoxynucleotides on the differentiation of Treg/ Th17 cells. Molecular Immunology. 2021, 132, 199—208, DOI: 10.1016/j.molimm.2021.01.003.
  13. Qu Y., Jiang Z., Chen Z., Luo S., Xie B., Wu X., et al. CpG-oligodeoxynucleotides challenged macrophages ameliorate acetaminophen induced liver injury by activating TLR9/IRG1/ itaconate me­tabolic pathway. Molecular Medicine, 2025, 31(1), 282, DOI: 10.1186/s10020-025-01324-0.
  14. Lamphier M. S., Sirois C. M., Verma A., Golenbock D. T., Latz E. TLR9 and the recognition of self and non-self nucleic acids. Ann. N. Y. Acad. Sci. 2006, 1082(1), 31—43, DOI: 10.1196/annals.1348.005.
  15. Tilstra J. S., John S., Gordon R. A., Leibler C., Kashgarian M., Bastacky S., et al. B cell–intrinsic TLR9 expression is protective in murine lupus. J. Clin. Invest. 2020, 130(6), 3172– 3187, DOI: 10.1172/JCI132328.
  16. You K., Gu H., Yuan Z., Xu X. Tumor Necrosis Factor Alpha Signaling and Organogenesis. Front. Cell Dev. Biol. 2021, 9, 727075, DOI: 10.3389/fcell.2021.727075.
  17. Xin Y., Gao X., Wang W., Xu X., Yu L., Ju X., et al. Circulating cell-free DNA indicates M1/M2 responses during septic peritonitis. Biochem. Biophys. Res. Commun. 2016, 477(4), 589—594, DOI: 10.1016/j.bbrc.2016.06.092.
  18. Tamkovich S. N., Litviakov N., Bryzgunova O. E., Dobrodeev A. Yu., Rykova E. Y., Tu­zi­kov S. A., et al. Cell-Surface-Bound Circulating DNA as a Prognostic Factor in Lung Can­cer. Ann. N. Y. Acad. Sci. 2008, 1137, 214—217, DOI: 10.1196/annals.1448.042.
  19. Демченко Е. Н., Гаврилова Е. Д., Гойман Е. В., Вольский Н. Н., Козлов В. А. Динамика уровня внеклеточной ДНК в ЛПС-индуцированной модели воспаления in vivo. Российский иммунологический журнал. 2022, 25(4), 423—430, DOI: 46235/1028-7221-1179-DOC.
  20. Демченко Е. Н., Гаврилова Е. Д., Гойман Е. В., Вольский Н. Н., Колесникова О. П., Козлов В. А. Внеклеточная ДНК в крови как показатель воспалительной реакции in vivo. Медицинская иммунология. 2022, 24(4), 853—860, DOI: 10.15789/1563-0625-EDI-2504.
  21. Demchenko E. N., Gavrilova E. D., Goiman E. V., Volsky N. N. Fatty acid receptor GPR84 and Th1/Th2 balance in the experimental system in vivo. Medical Immunology (Russia). 2021, 23(4), 659— 664, DOI: 10.15789/1563-0625-FAR-2235.
  22. Gavrilova E. D., Goiman E. V., Derzhalova A. S., Stetsenko D. A., Burakova E. A. Effects of Immunosuppressive Oligonucleotides A151, ODN4084-F, and μ-ODN4084-F on Mitigation of Acute Graft-Versus-Host Disease in Experimental Model. Cytokines and inflammation. 2024, 21(3), 135—143, DOI: 10.17816/CI642255.
  23. Jakob T., Walker P. S., Krieg A. M., Udey M. C., Vogel J. C. Activation of cutaneous dendritic cells by CpG-containing oligodeoxynucleotides: a role for dendritic cells in the augmentation of Th1 responses by immunostimulatory DNA. J. Immunol. 1998, 161(6), 3042—3049.
  24. Hayashi T., Beck L., Rossetto C., Gong X., Takikawa O., Takabayashi K., et al. Inhibition of expe­rimental asthma by indoleamine 2,3-dioxygenase. J. Clin. Invest. 2004, 114(2), 270—279, DOI: 10.1172/JCI21275.
  25. Christensen S. R., Shupe J., Nickerson K., Kashgarian M., Flavell R. A., Shlomchik M. J. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and reg­ulatory roles in a murine model of lupus. Immunity. 2006, 25(3), 417—428, DOI: 10.1016/j.immu­ni.2006.07.013.