High macrophage activities are associated with advanced periductal fibrosis in chronic Opisthorchis viverrini infection



Salao, Kanin, Watakulsin, Krongkarn, Mairiang, Eimorn, Suttiprapa, Sutas, Tangkawattana, Sirikachorn, Edwards, Steven W ORCID: 0000-0002-7074-0552 and Sripa, Banchob
(2018) High macrophage activities are associated with advanced periductal fibrosis in chronic Opisthorchis viverrini infection. PARASITE IMMUNOLOGY, 41 (1). e12603-.

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Abstract

Liver fluke infection caused by Opisthorchis viverrini induces several hepatobiliary conditions including advanced periductal fibrosis (APF ) and cholangiocarcinoma (CCA ), but >25% of the infected population develops APF and 1% develop CCA . The innate immune response is the first line of defence, and macrophages are critical regulators of fibrosis. We hypothesized that macrophages from infected individuals have different capacities to either promote or suppress periductal fibrosis. We compared phagocytic activities of macrophages of healthy individuals and O viverrini‐ infected individuals ± APF , and found that macrophages from infected individuals with APF ingested significantly higher numbers of beads compared with healthy controls and O viverrini‐ infected individuals without APF . To further investigate proteolytic activity, we monitored real‐time phagosomal proteolysis of beads conjugated to DQ ‐BODIPY ‐BSA using live cell imaging. We show that macrophages from O viverrini‐ infected individuals with APF also have elevated phagosomal proteolysis activity, which is consistent with their increased phagocytic activity. Additionally, stimulated ROS production by blood monocytes was higher in individuals with APF compared with healthy controls and infected individuals without APF . These results suggest that during O viverrini infection, macrophages with high phagocytic and proteolytic activities together with elevated ROS production are the phenotypes that can promote tissue damage, which results in periductal fibrosis.

Item Type: Article
Uncontrolled Keywords: flow cytometry, human, innate immunity, Opisthorchis viverrini, peripheral blood mononuclear cells, macrophages
Depositing User: Symplectic Admin
Date Deposited: 24 May 2019 11:58
Last Modified: 19 Jan 2023 00:43
DOI: 10.1111/pim.12603
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3042477