The microglial NLRP3 inflammasome is involved in human SARS-CoV-2 cerebral pathogenicity: A report of three post-mortem cases

We herein report, by using confocal immunofluorescence, the colocalization of the SARS-CoV-2 nucleocapsid within neurons, astrocytes, oligodendrocytes and microglia in three deceased COVID-19 cases, of between 78 and 85 years of age at death. The viral nucleocapsid was detected together with its ACE...

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Bibliographic Details
Published in:	Journal of neuroimmunology Vol. 361; p. 577728
Main Authors:	Cama, Viviana Falcón, Marín-Prida, Javier, Acosta-Rivero, Nelson, Acosta, Emilio F., Díaz, Leonardo Oramas, Casadesús, Ana V., Fernández-Marrero, Briandy, Gilva-Rodríguez, Nathalie, Cremata-García, Daina, Cervantes-Llanos, Majel, Piniella-Matamoros, Beatriz, Sánchez, Daisy, del Rosario-Cruz, Leticia, Borrajero, Israel, Díaz, Angelina, González, Yorexis, Pentón-Arias, Eduardo, Montero-González, Teresita, Guillen-Nieto, Gerardo, Pentón-Rol, Giselle
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 15-12-2021
Subjects:	Aged Aged, 80 and over Astrocytes - virology Autopsy Brain - immunology Brain - pathology Brain - virology COVID-19 COVID-19 - immunology COVID-19 - pathology COVID-19 - virology Female Human brain Humans Inflammasomes - immunology Macrophages Male Microglia - immunology Microglia - virology Neurons - virology NLR Family, Pyrin Domain-Containing 3 Protein - immunology NLRP3 inflammasome Nucleocapsid Oligodendroglia - virology SARS-CoV-2 SARS-CoV-2 - pathogenicity Short Communication COVID-19 ACE2 SARS-CoV-2 NC Human brain CNS NLRP3 inflammasome Macrophages
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Summary:	We herein report, by using confocal immunofluorescence, the colocalization of the SARS-CoV-2 nucleocapsid within neurons, astrocytes, oligodendrocytes and microglia in three deceased COVID-19 cases, of between 78 and 85 years of age at death. The viral nucleocapsid was detected together with its ACE2 cell entry receptor, as well as the NLRP3 inflammasome in cerebral cortical tissues. It is noteworthy that NLRP3 was colocalized with CD68 + macrophages in the brain and lung of the deceased, suggesting the critical role of this type of inflammasome in SARS-CoV-2 lesions of the nervous system/lungs and supporting its potential role as a therapeutic target. [Display omitted] •SARS-CoV-2 infects multiple cell types in human cerebral cortex.•CD68+ virus-infected microglia and lung macrophages activate NLRP3 inflammasome.•Inhibition of NLRP3 inflammasome could improve COVID-19 neurological complications.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3 These authors contributed equally to this study and should be considered as co-first authors.
ISSN:	0165-5728 1872-8421
DOI:	10.1016/j.jneuroim.2021.577728