SYNERGISTIC INTERACTIONS OF NOD1 AND TLR4 RECEPTORS OF INNATE IMMUNITY

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Abstract

We performed a simultaneous analysis of cytokine expression and metabolic reprogramming of macrophages upon combined stimulation of NOD1 and TLR4 receptors of innate immunity. NOD1 and TLR4 agonists boosted main parameters of glycolysis (extracellular acidification rate, glucose consumption, lactate release). However, changes of these parameters upon combined stimulation were not greater than those induced by stimulation of each individual receptor. At the same time, combined stimulation synergistically induced pro-inflammatory cytokine production and mRNA expression at relatively late time points (4–9 hours) after addition of agonists. In all, metabolic reprogramming may support synergistic induction of cytokines upon combined NOD1 and TLR4 stimulation; however, the origin of this synergy is in the synergistic induction of cytokine gene expression.

About the authors

N. E. Murugina

National Research Center “Institute of Immunology” of the Federal Medical-Biological Agency of Russia

Author for correspondence.
Email: fake@neicon.ru

junior researcher, Laboratory of Clinical Immunology,

Moscow

Russian Federation

A. S. Budikhina

National Research Center “Institute of Immunology” of the Federal Medical-Biological Agency of Russia

Email: fake@neicon.ru

PhD, researcher, Laboratory of Clinical Immunology, 

Moscow

Russian Federation

P. V. Maximchik

Lomonosov Moscow State University

Email: fake@neicon.ru

PhD, researcher, Faculty of Fundamental Medicine,

Moscow

Russian Federation

Y. A. Dagil

National Research Center “Institute of Immunology” of the Federal Medical-Biological Agency of Russia

Email: fake@neicon.ru

researcher, Laboratory of Clinical Immunology, 

Moscow

Russian Federation

L. S. Balyasova

National Research Center “Institute of Immunology” of the Federal Medical-Biological Agency of Russia

Email: fake@neicon.ru

junior researcher, Laboratory of Clinical Immunology,

Moscow

Russian Federation

V. V. Murugin

National Research Center “Institute of Immunology” of the Federal Medical-Biological Agency of Russia

Email: fake@neicon.ru

PhD, researcher, Laboratory of Clinical Immunology,

Moscow

Russian Federation

G. Z. Chkadua

FSBI “N. N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation

Email: fake@neicon.ru

PhD, senior researcher, Laboratory of experimental diagnostics and biotherapy of tumors,

Moscow

Russian Federation

B. V. Pinegin

National Research Center “Institute of Immunology” of the Federal Medical-Biological Agency of Russia

Email: fake@neicon.ru

Professor, Doctor of medical sciences, Head of the Department of immunodiagnostics and immunocorrection,

Moscow

Russian Federation

M. V. Pashenkov

National Research Center “Institute of Immunology” of the Federal Medical-Biological Agency of Russia

Email: mvpashenkov@yandex.ru

Doctor of medical sciences, Acting head of the Laboratory of Clinical Immunology, 

Moscow

Russian Federation

References

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  2. Van Heel D. A., Ghosh S., Butler M., Hunt K., Foxwell B. M.G., Mengin-Lecreulx D., Playford R. J. Synergistic enhancement of Toll-like receptor responses by NOD1 activation. Eur J Immunol. 2005, 35, 2471– 2476
  3. Fritz J. H., Girardin S. E., Fitting C., Werts C., MenginLecreulx D., Caroff M., Cavaillon J-M., Philpott D. J. and Adib-Conquy M. Synergistic stimulation of human monocytes and dendritic cells by Toll-like receptor 4 and NOD1- and NOD2-activating agonists. Eur J Immunol. 2005, 35 (8), 2459–70.
  4. O’Neill L. A., Pearce E. J. Immunometabolism governs dendritic cell and macrophage function. J Exp Med 2015, 213, 15–23.

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Copyright (c) 2019 Murugina N.E., Budikhina A.S., Maximchik P.V., Dagil Y.A., Balyasova L.S., Murugin V.V., Chkadua G.Z., Pinegin B.V., Pashenkov M.V.

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