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Grant support

I.T. was supported by Fomento de Investigacion and FPI-UAM fellowships by Universidad Autonoma de Madrid. E.M.G. and I.T. were funded by PID2021-127899OB-I00 Generacion de Conocimiento and CNS2023-144841 consolidacion investigadora grants from Agencia Estatal de Investigacion. E.M.G. and C.D.A. were also supported by RYC2018-024374-I. Ramon y Cajal Program. E.M.G., M.J.B., and M.G. were supported by REDINCOV by la MARAT TV3 (202104-30-31) and La Caixa Foundation HR20-00218. E.M.G., I.S. and I.S.C. were funded by CIBERINFECC from Instituto de Salud Carlos III. O.P. was supported by REDINCOV. MCM was supported by La Caixa Banking Foundation LCF/PR/HR20-00218. IGA was supported by PEARL thanks to grants RD16/0011/0012 and PI18/0371 from the Ministerio de Economia y Competitividad (Instituto de Salud Carlos III) and co-funded by Fondo Europeo de Desarrollo Regional (FEDER). I.S.C. was supported by the Rio Hortega Grant program (CM21/00157) and CIBERINFECC from Instituto de Salud Carlos III. F.S.M., A.A. were supported by INMUNOVACTER REACT-EU grant from Comunidad de Madrid. F.S.M. was also supported by grants PDC2021-121719-I00 and PID-2020-120412RB-I00 from the Spanish Ministry of Economy and Competitiveness (MINECO). M.J.B. is supported by the Agencia Estatal de Investigacion project PID2021-123321OB-I00 funded by MCIN /AEI /10.13039/501100011033/ FEDER, UE; the Gilead Fellowship GLD22/00152, and the Miguel Servet program funded by the Spanish Health Institute Carlos III (CPII22/00005). N.M.C. was supported by S2022/BMD-7209 (INTEGRAMUNE-CM) to N.M.C. C.M.C. was supported by FIS.18/01163. F.S.M. and N.M.C. were also supported by La Caixa Health Research Grant LCF/PR/HR23/52430018. Grants to A.A. from the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III, co-funded by the Fondo Europeo de Desarrollo Regional (FEDER) (FIS PI19/00549; FIS PI22/01542), and Sociedad Cooperativa de Viviendas Buen Suceso, S. Coop. Mad; to A.A. and F.S.M. from the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III, co-funded by the Fondo Europeo de Desarrollo Regional (FEDER) (CIBER Cardiovascular). A.A. was supported by CIBER cardiovascular (CIBERCV) from Instituto de Salud Carlos III. L.E.P. was financed by Inmunovacter REACT-UE (Comunidad de Madrid). We also would like to thank Veronica Labrador from the Microscopy Core from Centro Nacional de Investigaciones Cardiovasculares for technical support in confocal image analysis.

Analysis of institutional authors

Tsukalov, IlyaAuthorRajas, OlgaAuthorMartín-Cófreces, NoaAuthorDe Los Santos, IgnacioAuthorMunoz-Calleja, CeciliaAuthorJose Calzada, MariaAuthorAlfranca, ArantzazuAuthorAncochea, JulioAuthorSanchez-Madrid, FranciscoAuthorMartin-Gayo, EnriqueCorresponding Author

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October 14, 2024
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Article
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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

Publicated to:Nature Communications. 15 (1): 2100- - 2024-03-07 15(1), DOI: 10.1038/s41467-024-46322-8

Authors: Tsukalov, Ilya; Sanchez-Cerrillo, Ildefonso; Rajas, Olga; Avalos, Elena; Iturricastillo, Gorane; Esparcia, Laura; Jose Buzon, Maria; Genesca, Meritxell; Scagnetti, Camila; Popova, Olga; Martin-Cofreces, Noa; Calvet-Mirabent, Marta; Marcos-Jimenez, Ana; Martinez-Fleta, Pedro; Delgado-Arevalo, Cristina; de los Santos, Ignacio; Munoz-Calleja, Cecilia; Jose Calzada, Maria; Gonzalez lvaro, Isidoro; Palacios-Calvo, Jose; Alfranca, Arantzazu; Ancochea, Julio; Sanchez-Madrid, Francisco; Martin-Gayo, Enrique

Affiliations

Hosp Univ La Princesa, Infect Dis Unit, Madrid, Spain - Author
Hosp Univ La Princesa, Inst Invest Sanitaria Princesa IIS IP, Immunol Unit, Madrid, Spain - Author
Hosp Univ La Princesa, Pneumol Unit, Madrid, Spain - Author
Hosp Univ La Princesa, Rheumatol Dept, Inst Invest Sanitaria Princesa IISIP, Madrid, Spain - Author
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain - Author
Inst Salud Carlos III, CIBER Infect Dis CIBERINFECC, Madrid, Spain - Author
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain - Author
Univ Alcala, Hosp Univ Ramon y Cajal, Inst Ramon Cajal Invest Sanitarias IRYCIS, Dept Pathol,Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain - Author
Univ Autonoma Barcelona, Inst Recerca Hosp Univ Vall dHebron VHIR, Dept Infect Dis, Barcelona, Spain - Author
Univ Autonoma Madrid, Med Fac, Madrid, Spain - Author
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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 NF kappa B-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.

Keywords

Calcium-binding proteinsCard signaling adaptor proteinsCd4(+) t-cellsCovid-1Covid-19ExpressionFateHumansImmunityInfectionInflammasomesMonocytesNfkb1 protein, humanNlr family, pyrin domain-containing 3 proteinNlrc4Nlrc4 protein, humanNlrp3 inflammasomeNlrp3 protein, humanNucleoproteinsParthenolideSars-cov-2Transcription

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Nature Communications due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 8/134, thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary Sciences. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-07-09:

  • Google Scholar: 5
  • WoS: 6
  • Scopus: 6
  • Europe PMC: 3

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-09:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 15.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 18 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 17.5.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).
  • The number of mentions in news outlets: 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/712967

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (TSUKALOV, ILYA) and Last Author (MARTIN GAYO, ENRIQUE).

the author responsible for correspondence tasks has been MARTIN GAYO, ENRIQUE.