Inflammasome Activation in Human Liver Parenchyma During Severe Yellow Fever Inflammasome in Fatal Yellow Fever
Vanessa do Socorro Cabral Mirandaa, Luiz Fábio Magno Falcãob, Luis Arthur Moreira Ferreirab, Lucas Correa Modestob, Pablo Rodrigues Nunes de Souzab, Rafael Malcher Meira Rochab, Arnaldo Jorge Martins Filhoa, Jorge Rodrigues de Sousaa, Mayumi Duarte Wakimotoc, Pedro Fernando da Costa Vasconcelosa, Carla Pagliarid,
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Abstract
Background: Yellow fever virus (YFV) infection causes severe liver damage, yet the specific immunopathological mechanisms remain partially unclear. This study investigated the contribution of the inflammasome complex to the pathogenesis of fatal yellow fever (YF) in human liver tissue. Methods: We analyzed liver tissue samples from 21 patients with fatal YFV infection and five flavivirus-negative controls. Immunohistochemical analysis was performed to detect receptors (NLRP1, NLRP3, AIM2), cytokines (IL-1β, IL-18, IL-33), and enzymes (caspase 1, iNOS, arginase 1). Results: Upregulation of NLRP1, NLRP3, and AIM2 receptors, along with increased expression of IL-1β, IL-18, IL-33, caspase 1, iNOS, and arginase 1, was observed in infected tissues compared to controls. These markers were predominantly expressed in the midzonal region. Statistical analysis revealed strong correlations among these markers across hepatic zones. Conclusion: The findings demonstrate that inflammasome activation is associated with a robust inflammatory response in fatal human YF cases. The midzonal zone acts as a critical area for the production of inflammatory markers, suggesting a key role for the inflammasome in YFV-induced liver pathology.