Role of Th17 Cytokines in the Liver's Immune Response during Fatal Yellow Fever: Triggering Cell Damage Mechanisms.
Marcos Luiz Gaia CarvalhoLuiz Fábio Magno FalcãoJeferson da Costa LopesCaio Cesar Henriques MendesFábio Alves OlímpioVanessa do Socorro Cabral MirandaLais Carneiro Dos SantosDaniel Dias Pinheiro de MoraesMarcos Virgilio Bertonsin FilhoLuccas Delgado da CostaRaimunda do Socorro da Silva AzevedoAna Cecília Ribeiro CruzVanessa Costa Alves GalúcioLívia Caricio MartinsMaria Irma Seixas DuarteArnaldo Jorge Martins FilhoJorge Rodrigues de SousaPedro Fernando da Costa VasconcelosJuarez Antônio Simões QuaresmaPublished in: Cells (2022)
Yellow fever (YF) is an infectious and acute viral haemorrhagic disease that triggers a cascade of host immune responses. We investigated the Th17 cytokine profile in the liver tissue of patients with fatal YF. Liver tissue samples were collected from 26 deceased patients, including 21 YF-positive and 5 flavivirus-negative patients, with preserved hepatic parenchyma architecture, who died of other causes. Histopathological and immunohistochemical analysis were performed on the liver samples to evaluate the Th17 profiles (ROR-γ, STAT3, IL-6, TGF-β, IL-17A, and IL-23). Substantial differences were found in the expression levels of these markers between the patients with fatal YF and controls. A predominant expression of Th17 cytokine markers was observed in the midzonal region of the YF cases, the most affected area in the liver acinus, compared with the controls. Histopathological changes in the hepatic parenchyma revealed cellular damage characterised mainly by the presence of inflammatory cell infiltrates, Councilman bodies (apoptotic cells), micro/macrovesicular steatosis, and lytic and coagulative necrosis. Hence, Th17 cytokines play a pivotal role in the immunopathogenesis of YF and contribute markedly to triggering cell damage in patients with fatal disease outcomes.