Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2
In the wake of the COVID-19 pandemic caused by SARS-CoV-2, questions emerged about the potential effects of Bacillus Calmette-Guérin (BCG) vaccine on the immune response to SARS-CoV-2 infection, including the neurodegenerative diseases it may contribute to. To explore this, an experimental study was...
| Autores: | , , , , , , , , , , , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/379566 |
| Acesso em linha: | http://hdl.handle.net/10261/379566 |
| Access Level: | acceso abierto |
| Palavra-chave: | BCG stimulation K18-hACE2 SARS-CoV-2 Neuroinvasion |
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Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2Sánchez-Morales, LidiaPorras, NéstorGarcía-Seco, TeresaPérez-Sancho, MartaCruz, FátimaChinchilla, BlancaBarroso-Arévalo, SandraDíaz-Frutos, MartaBuendía-Andrés, AránzazuMoreno, InmaculadaBriones, VíctorRisalde, María ÁngelesFuente, José de laJuste, Ramón A.Garrido, Joseba M.Balseiro, AnaGortázar, ChristianRodríguez-Bertos, AntonioDomínguez, MercedesDomínguez, LucasBCG stimulationK18-hACE2SARS-CoV-2NeuroinvasionIn the wake of the COVID-19 pandemic caused by SARS-CoV-2, questions emerged about the potential effects of Bacillus Calmette-Guérin (BCG) vaccine on the immune response to SARS-CoV-2 infection, including the neurodegenerative diseases it may contribute to. To explore this, an experimental study was carried out in BCG-stimulated and non-stimulated k18-hACE2 mice challenged with SARS-CoV-2. Viral loads in tissues determined by RT-qPCR, histopathology in brain and lungs, immunohistochemical study in brain (IHC) as well as mortality rates, clinical signs and plasma inflammatory and coagulation biomarkers were assessed. Our results showed BCG-SARS-CoV-2 challenged mice presented higher viral loads in the brain and an increased frequency of neuroinvasion, with the greatest differences observed between groups at 3-4 days post-infection (dpi). Histopathological examination showed a higher severity of brain lesions in BCG-SARS-CoV-2 challenged mice, mainly consisting of neuroinflammation, increased glial cell population and neuronal degeneration, from 5 dpi onwards. This group also presented higher interstitial pneumonia and vascular thrombosis in lungs (3-4 dpi), BCG-SARS-CoV-2 mice showed higher values for TNF-α and D-dimer values, while iNOS values were higher in SARS-CoV-2 mice at 3-4 dpi. Results presented in this study indicate that BCG stimulation could have intensified the inflammatory and neurodegenerative lesions promoting virus neuroinvasion and dissemination in this experimental model. Although k18-hACE2 mice show higher hACE2 expression and neurodissemination, this study suggests that, although the benefits of BCG on enhancing heterologous protection against pathogens and tumour cells have been broadly demonstrated, potential adverse outcomes due to the non-specific effects of BCG should be considered.This research was partially funded by a REACT-European Union grant from the Comunidad de Madrid to the ANTICIPA project of Complutense University of Madrid (reference PR38/21) and partially funded by PID2020-112966RB-I00 financed by MCIN/AEI/10.13039/501100011033.Peer reviewedBioMed CentralEuropean CommissionComunidad de MadridUniversidad Complutense de MadridAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/379566reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-112966RB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1186/s13567-024-01325-7https://doi.org/10.1186/s13567-024-01325-7Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3795662026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2 |
| title |
Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2 |
| spellingShingle |
Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2 Sánchez-Morales, Lidia BCG stimulation K18-hACE2 SARS-CoV-2 Neuroinvasion |
| title_short |
Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2 |
| title_full |
Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2 |
| title_fullStr |
Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2 |
| title_full_unstemmed |
Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2 |
| title_sort |
Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2 |
| dc.creator.none.fl_str_mv |
Sánchez-Morales, Lidia Porras, Néstor García-Seco, Teresa Pérez-Sancho, Marta Cruz, Fátima Chinchilla, Blanca Barroso-Arévalo, Sandra Díaz-Frutos, Marta Buendía-Andrés, Aránzazu Moreno, Inmaculada Briones, Víctor Risalde, María Ángeles Fuente, José de la Juste, Ramón A. Garrido, Joseba M. Balseiro, Ana Gortázar, Christian Rodríguez-Bertos, Antonio Domínguez, Mercedes Domínguez, Lucas |
| author |
Sánchez-Morales, Lidia |
| author_facet |
Sánchez-Morales, Lidia Porras, Néstor García-Seco, Teresa Pérez-Sancho, Marta Cruz, Fátima Chinchilla, Blanca Barroso-Arévalo, Sandra Díaz-Frutos, Marta Buendía-Andrés, Aránzazu Moreno, Inmaculada Briones, Víctor Risalde, María Ángeles Fuente, José de la Juste, Ramón A. Garrido, Joseba M. Balseiro, Ana Gortázar, Christian Rodríguez-Bertos, Antonio Domínguez, Mercedes Domínguez, Lucas |
| author_role |
author |
| author2 |
Porras, Néstor García-Seco, Teresa Pérez-Sancho, Marta Cruz, Fátima Chinchilla, Blanca Barroso-Arévalo, Sandra Díaz-Frutos, Marta Buendía-Andrés, Aránzazu Moreno, Inmaculada Briones, Víctor Risalde, María Ángeles Fuente, José de la Juste, Ramón A. Garrido, Joseba M. Balseiro, Ana Gortázar, Christian Rodríguez-Bertos, Antonio Domínguez, Mercedes Domínguez, Lucas |
| author2_role |
author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
European Commission Comunidad de Madrid Universidad Complutense de Madrid Agencia Estatal de Investigación (España) Ministerio de Ciencia, Innovación y Universidades (España) Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
BCG stimulation K18-hACE2 SARS-CoV-2 Neuroinvasion |
| topic |
BCG stimulation K18-hACE2 SARS-CoV-2 Neuroinvasion |
| description |
In the wake of the COVID-19 pandemic caused by SARS-CoV-2, questions emerged about the potential effects of Bacillus Calmette-Guérin (BCG) vaccine on the immune response to SARS-CoV-2 infection, including the neurodegenerative diseases it may contribute to. To explore this, an experimental study was carried out in BCG-stimulated and non-stimulated k18-hACE2 mice challenged with SARS-CoV-2. Viral loads in tissues determined by RT-qPCR, histopathology in brain and lungs, immunohistochemical study in brain (IHC) as well as mortality rates, clinical signs and plasma inflammatory and coagulation biomarkers were assessed. Our results showed BCG-SARS-CoV-2 challenged mice presented higher viral loads in the brain and an increased frequency of neuroinvasion, with the greatest differences observed between groups at 3-4 days post-infection (dpi). Histopathological examination showed a higher severity of brain lesions in BCG-SARS-CoV-2 challenged mice, mainly consisting of neuroinflammation, increased glial cell population and neuronal degeneration, from 5 dpi onwards. This group also presented higher interstitial pneumonia and vascular thrombosis in lungs (3-4 dpi), BCG-SARS-CoV-2 mice showed higher values for TNF-α and D-dimer values, while iNOS values were higher in SARS-CoV-2 mice at 3-4 dpi. Results presented in this study indicate that BCG stimulation could have intensified the inflammatory and neurodegenerative lesions promoting virus neuroinvasion and dissemination in this experimental model. Although k18-hACE2 mice show higher hACE2 expression and neurodissemination, this study suggests that, although the benefits of BCG on enhancing heterologous protection against pathogens and tumour cells have been broadly demonstrated, potential adverse outcomes due to the non-specific effects of BCG should be considered. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10261/379566 |
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http://hdl.handle.net/10261/379566 |
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Inglés |
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Inglés |
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#PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-112966RB-I00 The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1186/s13567-024-01325-7 https://doi.org/10.1186/s13567-024-01325-7 Sí |
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info:eu-repo/semantics/openAccess |
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openAccess |
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BioMed Central |
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BioMed Central |
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