Cells (Jun 2022)

Role of Th17 Cytokines in the Liver’s Immune Response during Fatal Yellow Fever: Triggering Cell Damage Mechanisms

  • Marcos Luiz Gaia Carvalho,
  • Luiz Fábio Magno Falcão,
  • Jeferson da Costa Lopes,
  • Caio Cesar Henriques Mendes,
  • Fábio Alves Olímpio,
  • Vanessa do Socorro Cabral Miranda,
  • Lais Carneiro dos Santos,
  • Daniel Dias Pinheiro de Moraes,
  • Marcos Virgilio Bertonsin Filho,
  • Luccas Delgado da Costa,
  • Raimunda do Socorro da Silva Azevedo,
  • Ana Cecília Ribeiro Cruz,
  • Vanessa Costa Alves Galúcio,
  • Lívia Caricio Martins,
  • Maria Irma Seixas Duarte,
  • Arnaldo Jorge Martins Filho,
  • Jorge Rodrigues de Sousa,
  • Pedro Fernando da Costa Vasconcelos,
  • Juarez Antônio Simões Quaresma

DOI
https://doi.org/10.3390/cells11132053
Journal volume & issue
Vol. 11, no. 13
p. 2053

Abstract

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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.

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