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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1448515
This article is part of the Research Topic Unraveling the Molecular Mechanisms of Cytokine Signaling in Regulating Inflammatory Diseases View all 12 articles

Cytokine production in an ex vivo model of SARS-CoV-2 lung infection

Provisionally accepted
Daria A. Vorobyeva Daria A. Vorobyeva 1,2Daria M. Potashnikova Daria M. Potashnikova 1,2*Elena V. Maryukhnich Elena V. Maryukhnich 1,2*George I. Rusakovich George I. Rusakovich 1Anna V. Tvorogova Anna V. Tvorogova 1Anna I. Kalinskaya Anna I. Kalinskaya 1,2Natalia V. Pinegina Natalia V. Pinegina 1,2*Anna V. Kovyrshina Anna V. Kovyrshina 3Inna V. Dolzhikova Inna V. Dolzhikova 3*Alexander B. Postnikov Alexander B. Postnikov 4*Fedor N. Rozov Fedor N. Rozov 4*Tatiana N. Sotnikova Tatiana N. Sotnikova 1*Dmitry Y. Kanner Dmitry Y. Kanner 5*Denis Y. Logunov Denis Y. Logunov 3*Alexander L. Gintsburg Alexander L. Gintsburg 3*Elena J. Vasilieva Elena J. Vasilieva 1,2Leonid B. Margolis Leonid B. Margolis 6*
  • 1 City Clinical Hospital named after I.V. Davydovsky, Moscow, Russia
  • 2 FSBEI HE “Russian University of Medicine” of the Ministry of Health of the Russian Federation, Moscow, Russia, Moscow, Russia
  • 3 N.F.Gamaleya Scientific Research Institute of Epidemiology and Microbiology, Russian Academy of Medical Sciences, Moscow, Moscow Oblast, Russia
  • 4 HyTest (Finland), Turku, Finland
  • 5 Moscow City Oncology Hospital No. 62, Moscow, Moscow Oblast, Russia
  • 6 Faculty of Natural Sciences and Medicine, Ilia State University, Tbilisi, Georgia

The final, formatted version of the article will be published soon.

    The mechanisms of the SARS-CoV-2-triggered complex alterations in immune cell activation and production of cytokines in lung tissue remain poorly understood, in part because of the limited use of adequate tissue models that simulate the structure and cell composition of the lung in vivo. We developed a novel ex vivo model of SARS-CoV-2 infection of lung explants, that maintains the intact tissue composition and the viral load for up to 7-10 days. Using this model, we studied cytokine production during SARS-CoV-2 infection. We measured a panel of 41 cytokines using xMAP technology, finding an elevation in concentrations of G-CSF, GM-CSF, GRO-α, IFN-γ, IL-6, IL-8, IP-10, MCP-3, MIP-1α, PDGF-AA, and VEGF, and a decrease of IL-1RA concentration in infected tissue in comparison with non-infected explant tissue. These results generally reflect the data obtained in COVID-19 patients. GRO-α, IFN-γ, IL-6, IL-8, MCP-1, MCP-3, and RANTES correlated with the viral load, forming a distinct cluster. In conclusion, our lung ex vivo model faithfully reproduces some aspects of cytokine alterations in COVID-19 patients at an early stage of the disease, thus making the investigation of SARS-CoV-2 infection mechanisms more accessible and providing a potential platform for antiviral drug testing.

    Keywords: Ex vivo model, lung explant ex vivo culture, SARS-CoV-2, COVID-19, Cytokines, immune response, antiviral response

    Received: 13 Jun 2024; Accepted: 25 Sep 2024.

    Copyright: © 2024 Vorobyeva, Potashnikova, Maryukhnich, Rusakovich, Tvorogova, Kalinskaya, Pinegina, Kovyrshina, Dolzhikova, Postnikov, Rozov, Sotnikova, Kanner, Logunov, Gintsburg, Vasilieva and Margolis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Daria M. Potashnikova, City Clinical Hospital named after I.V. Davydovsky, Moscow, Russia
    Elena V. Maryukhnich, City Clinical Hospital named after I.V. Davydovsky, Moscow, Russia
    Natalia V. Pinegina, City Clinical Hospital named after I.V. Davydovsky, Moscow, Russia
    Inna V. Dolzhikova, N.F.Gamaleya Scientific Research Institute of Epidemiology and Microbiology, Russian Academy of Medical Sciences, Moscow, 123098, Moscow Oblast, Russia
    Alexander B. Postnikov, HyTest (Finland), Turku, Finland
    Fedor N. Rozov, HyTest (Finland), Turku, Finland
    Tatiana N. Sotnikova, City Clinical Hospital named after I.V. Davydovsky, Moscow, Russia
    Dmitry Y. Kanner, Moscow City Oncology Hospital No. 62, Moscow, 143423, Moscow Oblast, Russia
    Denis Y. Logunov, N.F.Gamaleya Scientific Research Institute of Epidemiology and Microbiology, Russian Academy of Medical Sciences, Moscow, 123098, Moscow Oblast, Russia
    Alexander L. Gintsburg, N.F.Gamaleya Scientific Research Institute of Epidemiology and Microbiology, Russian Academy of Medical Sciences, Moscow, 123098, Moscow Oblast, Russia
    Leonid B. Margolis, Faculty of Natural Sciences and Medicine, Ilia State University, Tbilisi, 0162, Georgia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.