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

Ilya Tsukalov, Ildefonso Sánchez-Cerrillo, Olga Rajas, Elena Avalos, Gorane Iturricastillo, Laura Esparcia, María José Buzón, Meritxell Genescà, Camila Scagnetti, Olga Popova, Noa Martin-Cófreces, Marta Calvet-Mirabent, Ana Marcos-Jimenez, Pedro Martínez-Fleta, Cristina Delgado-Arévalo, Ignacio los Santos, Cecilia Muñoz-Calleja, María José Calzada, Isidoro González Álvaro, José Palacios-Calvo, Arantzazu Alfranca, Julio Ancochea, Francisco Sánchez-Madrid and Enrique Martin-Gayo ()
Additional contact information
Ilya Tsukalov: Universidad Autónoma de Madrid
Ildefonso Sánchez-Cerrillo: Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP
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
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
Marta Calvet-Mirabent: Universidad Autónoma de Madrid
Ana Marcos-Jimenez: Universidad Autónoma de Madrid
Pedro Martínez-Fleta: Universidad Autónoma de Madrid
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
Cecilia Muñoz-Calleja: Immunology Unit from Hospital Universitario La Princesa, Instituto Investigación Sanitaria-Princesa IIS-IP
María José Calzada: Universidad Autónoma de Madrid
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
Julio Ancochea: Pneumology Unit from Hospital Universitario La Princesa
Francisco Sánchez-Madrid: Universidad Autónoma de Madrid
Enrique Martin-Gayo: Universidad Autónoma de Madrid

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-46322-8

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