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NFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins

Author

Listed:
  • Ilya Tsukalov

    (Universidad Autónoma de Madrid)

  • Ildefonso Sánchez-Cerrillo

    (Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP
    CIBER Infectious Diseases (CIBERINFECC), Instituto de Salud Carlos III)

  • Olga Rajas

    (Pneumology Unit from Hospital Universitario La Princesa)

  • Elena Avalos

    (Pneumology Unit from Hospital Universitario La Princesa)

  • Gorane Iturricastillo

    (Pneumology Unit from Hospital Universitario La Princesa)

  • Laura Esparcia

    (Universidad Autónoma de Madrid
    Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP)

  • María José Buzón

    (Universitat Autònoma de Barcelona)

  • Meritxell Genescà

    (Universitat Autònoma de Barcelona)

  • Camila Scagnetti

    (Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP)

  • Olga Popova

    (Universidad Autónoma de Madrid)

  • Noa Martin-Cófreces

    (Universidad Autónoma de Madrid
    Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP)

  • Marta Calvet-Mirabent

    (Universidad Autónoma de Madrid
    Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP)

  • Ana Marcos-Jimenez

    (Universidad Autónoma de Madrid
    Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP)

  • Pedro Martínez-Fleta

    (Universidad Autónoma de Madrid
    Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP)

  • Cristina Delgado-Arévalo

    (Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP)

  • Ignacio los Santos

    (CIBER Infectious Diseases (CIBERINFECC), Instituto de Salud Carlos III
    Infectious Diseases Unit from Hospital Universitario La Princesa)

  • Cecilia Muñoz-Calleja

    (Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP
    CIBER Infectious Diseases (CIBERINFECC), Instituto de Salud Carlos III)

  • María José Calzada

    (Universidad Autónoma de Madrid
    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III)

  • Isidoro González Álvaro

    (Rheumatology Department from Hospital Universitario La Princesa. Instituto de Investigación Sanitaria-Princesa IIS-IP)

  • José Palacios-Calvo

    (Hospital Universitario Ramón y Cajal. Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Universidad de Alcalá. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC))

  • Arantzazu Alfranca

    (Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP
    CIBER Cardiovascular, Instituto de Salud Carlos III)

  • Julio Ancochea

    (Pneumology Unit from Hospital Universitario La Princesa)

  • Francisco Sánchez-Madrid

    (Universidad Autónoma de Madrid
    Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP
    CIBER Cardiovascular, Instituto de Salud Carlos III)

  • Enrique Martin-Gayo

    (Universidad Autónoma de Madrid
    Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP
    CIBER Infectious Diseases (CIBERINFECC), Instituto de Salud Carlos III)

Abstract

Increased recruitment of transitional and non-classical monocytes in the lung during SARS-CoV-2 infection is associated with COVID-19 severity. However, whether specific innate sensors mediate the activation or differentiation of monocytes in response to different SARS-CoV-2 proteins remain poorly characterized. Here, we show that SARS-CoV-2 Spike 1 but not nucleoprotein induce differentiation of monocytes into transitional or non-classical subsets from both peripheral blood and COVID-19 bronchoalveolar lavage samples in a NFκB-dependent manner, but this process does not require inflammasome activation. However, NLRP3 and NLRC4 differentially regulated CD86 expression in monocytes in response to Spike 1 and Nucleoprotein, respectively. Moreover, monocytes exposed to Spike 1 induce significantly higher proportions of Th1 and Th17 CD4 + T cells. In contrast, monocytes exposed to Nucleoprotein reduce the degranulation of CD8 + T cells from severe COVID-19 patients. Our study provides insights in the differential impact of innate sensors in regulating monocytes in response to different SARS-CoV-2 proteins, which might be useful to better understand COVID-19 immunopathology and identify therapeutic targets.

Suggested Citation

  • Ilya Tsukalov & Ildefonso Sánchez-Cerrillo & Olga Rajas & Elena Avalos & Gorane Iturricastillo & Laura Esparcia & María José Buzón & Meritxell Genescà & Camila Scagnetti & Olga Popova & Noa Martin-Cóf, 2024. "NFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46322-8
    DOI: 10.1038/s41467-024-46322-8
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    References listed on IDEAS

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    1. Fumitaka Hayashi & Kelly D. Smith & Adrian Ozinsky & Thomas R. Hawn & Eugene C. Yi & David R. Goodlett & Jimmy K. Eng & Shizuo Akira & David M. Underhill & Alan Aderem, 2001. "The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5," Nature, Nature, vol. 410(6832), pages 1099-1103, April.
    2. Qian Zhang & Paul Bastard & Aurélie Cobat & Jean-Laurent Casanova, 2022. "Human genetic and immunological determinants of critical COVID-19 pneumonia," Nature, Nature, vol. 603(7902), pages 587-598, March.
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