Open AccessChronic Hepatitis C: Conspectus of immunological events in the course of fibrosis evolution
Author(s) -
Dejan Baskić,
Vuk R. Vuković,
Suzana Popović,
Danijela Jovanović,
Slobodanka Mitrović,
Predrag Djurdjević,
Dusko Avramovic,
Aleksandra Arsovic,
Dragić Banković,
Jelena Čukić,
Željko Mijailović
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0219508
Subject(s) - fibrosis , immunology , immune system , cd8 , cytokine , proinflammatory cytokine , medicine , peripheral blood mononuclear cell , histopathology , pathology , biology , inflammation , biochemistry , in vitro
In chronically infected HCV patients emergence and evolution of fibrosis, as a consequence of virus persistence, can be considered as an indicator of disease advancement. Therefore the aim of this study was to correlate alterations of immune response in chronic HCV patients with liver histopathology. Sera cytokine levels and frequency of circulating and liver infiltrating cells were evaluated using 13plex Kit Flow Cytomix, flow cytometry and immunohistochemistry. We found that the number of circulating T lymphocytes (including CD4+, CD8+ and Treg) and B lymphocytes, as well as DCs, was higher in patients with no fibrosis than in healthy subjects. In patients with fibrosis frequency of these cells decreased, and contrarily, in the liver, number of T and B lymphocytes gradually increased with fibrosis. Importantly, in patients with advanced fibrosis, liver infiltrating regulatory T cells and DC-SIGN+ mononuclear cells with immunosuppressive and wound-healing effector functions were abundantly present. Cytokine profiling showed predominance of proinflammatory cytokines in patients with no fibrosis and a tendency of decline in level of all cytokines with severity of liver injury. Lower but sustained IL-4 production refers to Th2 predominance in higher stages of fibrosis. Altogether, our results reveal graduall alterations of immunological parameters during fibrosis evolution and illustrate the course of immunological events through disease progression.