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 MiggiolaroPublished 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.