ApoE deficiency promotes hepatic pathology by aggravating Th17/Treg imbalance in murine schistosomiasis japonica

Parasite Immunol. 2020 Dec;42(12):e12785. doi: 10.1111/pim.12785. Epub 2020 Sep 3.

Abstract

Aims: The Schistosoma japonicum (S japonicum)-infected ApoE gene deficiency (ApoE-/- ) mice were used to determine effect of ApoE on hepatic immunopathology.

Methods: Murine activities and appetite, body weight, and ratio of liver weight to its body weight (Hepatic mass index, HMI) were observed. Worm load and liver egg burden were evaluated as the infection intensity. Number and size of liver egg granulomas and serum levels of alanine aminotransferase (ALT) were investigated. We analysed hepatic fibrosis by markers of fibrosis in tissue, detected hepatic Th17 and Treg frequency by flow cytometry, and measured hepatic expressions of RORγt, Foxp3, IL-17A and TGF-β1 via qPCR. Lipid metabolism was determined by serum levels of cholesterol (TC) and triglyceride (TG) as well as hepatic Oil red O staining.

Results: In the infected ApoE-/- mice, the increased infection intensity aggravated the hepatic immunopathology (evidenced by increased HMI, elevated egg granulomas and increased ALT levels) and fibrosis (increased hepatic collagen deposition). ApoE deficiency resulted in significantly elevated ratio of hepatic Th17/Treg and higher serum levels of TC and TG, along with higher level of hepatic Oil red O staining.

Conclusions: ApoE deficiency promotes hepatic pathology and fibrosis by exacerbating Th17/Treg imbalance and altering lipid metabolism in murine schistosomiasis japonica.

Keywords: ApoE; Schistosoma japonicum; Th17/Treg; fibrosis; hepatic pathology; lipid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Female
  • Lipid Metabolism
  • Liver Cirrhosis / parasitology
  • Liver Cirrhosis / pathology
  • Mice
  • Parasite Load
  • Schistosoma japonicum / pathogenicity
  • Schistosomiasis japonica / immunology*
  • Schistosomiasis japonica / metabolism
  • Schistosomiasis japonica / parasitology
  • Schistosomiasis japonica / pathology*
  • T-Lymphocytes, Regulatory / pathology*
  • Th17 Cells / pathology*

Substances

  • Apolipoproteins E