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Lung Inflammasome Activation in SARS-CoV-2 Post-Mortem Biopsies.

Lucas Baena CarstensRaissa Campos D'amicoKaren Fernandes de MouraEduardo Morais de CastroFlávia Centenaro de OliveiraGiovanna Silva BarbosaGuilherme Vieira Cavalcante da SilvaIsadora BrennyJúlio César H DagostiniElisa Carolina HlatchukSabrina Pissette de LimaAna Paula Camargo MartinsMarina de Castro DeusCarolline Konzen KleinAna Paula Kubaski BenevidesSeigo NagashimaCleber Machado SouzaRicardo Aurino PinhoCristina Pellegrino BaenaAnna Flávia Ribeiro Dos Santos Miggiolaro
Published in: International journal of molecular sciences (2022)
The inflammasome complex is a key part of chronic diseases and acute infections, being responsible for cytokine release and cell death mechanism regulation. The SARS-CoV-2 infection is characterized by a dysregulated cytokine release. In this context, the inflammasome complex analysis within SARS-CoV-2 infection may prove beneficial to understand the disease's mechanisms. Post-mortem minimally invasive autopsies were performed in patients who died from COVID-19 ( n = 24), and lung samples were compared to a patient control group ( n = 11) and an Influenza A virus H1N1 subtype group from the 2009 pandemics ( n = 10). Histological analysis was performed using hematoxylin-eosin staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: ACE2, TLR4, NF-κB, NLRP-3 (or NALP), IL-1β, IL-18, ASC, CASP1, CASP9, GSDMD, NOX4, TNF-α. Data obtained from digital analysis underwent appropriate statistical tests. IHC analysis showed biomarkers that indicate inflammasome activation (ACE2; NF-κB; NOX4; ASC) were significantly increased in the COVID-19 group ( p < 0.05 for all) and biomarkers that indicate cell pyroptosis and inflammasome derived cytokines such as IL-18 ( p < 0.005) and CASP1 were greatly increased ( p < 0.0001) even when compared to the H1N1 group. We propose that the SARS-CoV-2 pathogenesis is connected to the inflammasome complex activation. Further studies are still warranted to elucidate the pathophysiology of the disease.
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