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Published on: February 10, 2015
[Effects of persistent Echinococcus multilocularis infections on hepatic fibrosis in mice]
Objective:
To investigate the effects of persistent Echinococcus multilocularis infections on hepatic fibrosis in mice, so as to provide insights into the understanding of liver fibrogenesis induced by E. multilocularis infections and the treatment of alveolar echinococcosis.
Methods:
Hepatic stellate HSC-T6 and LX-2 cells were exposed to the sera (25, 50 and 100 μL) from Meriones unguiculatus infected with E. multilocularis, and E. multilocularis, germinal layer cells (GCs) and protoscoleces (PSCs) for 48 hours, respectively. The cell proliferation was measured using a CCK-8 assay, and the levels of collagen 1 (Col1) and α-smooth muscle actin (α-SMA) were measured in the culture supernatant of HSC-T6 cells using ELISA. In addition, the serum and liver samples were collected 1, 2, 4, 6, 8 months post-infection with E. multilocularis, respectively. The serum Col1 and α-SMA concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and the deposition of collagen fibers was examined in mice livers using Sirius red staining.
Results:
The sera of E. multilocularis-infected gerbils promoted the proliferation of HSC-T6 and LX-2 cells in vitro, and there were significant differences seen in the proliferative rate of HSC-T6 (FHSC-T6 = 126.50, P < 0.05) and LX-2 cells (FLX-2 = 201.50, P < 0.05) among different serum groups, with the highest proliferative rate of HSC-T6 (573.36% ± 206.34%) and LX-2 cells (940.38% ± 61.65%) found following exposure to 100 μL mouse sera. Exposure to serum from E. multilocularis-infected gerbils resulted in an increase in the Col1 and α-SMA levels in the culture supernatant of HSC-T6 cells, with the greatest Col1 (20.99 ng/mL ± 2.01 ng/mL) and α-SMA levels (305.52 pg/mL ± 16.67 pg/mL) measured following exposure to 100 μL sera. The metacestodes (142.65% ± 9.17% and 189.99% ± 7.75%), GCs (118.55% ± 8.96% and 122.54% ± 0.21%) and PSCs of E. multilocularis (156.34% ± 17.45% and 160.59% ± 31.41%) all promoted the proliferation of HSC-T6 and LX-2 cells in vitro, and there were significant differences in the proliferative rates of HSC-T6 (FHSC-T6 = 11.24, P < 0.05) and LX-2 cells among groups (FLX-2 = 47.72, P < 0.05). Exposure to E. multilocularis resulted in an increase in Col1 and α-SMA levels in the culture supernatant of HSC-T6 cells, and the highest Col1 (4.43 ng/mL ± 2.23 ng/mL) and α-SMA levels (285.20 pg/mL ± 90.67 pg/mL) were detected following treatment with E. multilocularis metacestodes. In addition, a persistent increase was seen in the deposition of collagen fibers in mice livers 1 to 8 months post-infection with E. multilocularis, with the greatest Col1 level (280.26 ng/mL ± 23.04 ng/mL) seen 6 months post-infection and the highest α-SMA level (33.68 ng/mL ± 4.45 ng/mL) detected 8 months post-infection, respectively.
Conclusions:
Persistent E. multilocularis infections promote hepatic stellate cell proliferation, induce an increase in mouse serum Col1 and α-SMA levels, and cause elevated deposition of collagen fibers in mice livers. The infective stage of E. multilocularis is a critical period for inducing hepatic fibrosis of alveolar echinococcosis.
Insights
Persistent Echinococcus multilocularis infections promote liver fibrosis by increasing hepatic stellate cell proliferation and collagen deposition. This study highlights the infective stage
Area of Science:
- Parasitology
- Hepatology
- Immunology
Background:
- Alveolar echinococcosis, caused by Echinococcus multilocularis, is a severe parasitic disease characterized by liver damage.
- Hepatic fibrosis is a key pathological feature of chronic liver diseases, including alveolar echinococcosis.
- Understanding the mechanisms of liver fibrogenesis in E. multilocularis infections is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the impact of persistent Echinococcus multilocularis infections on hepatic fibrosis in a mouse model.
- To elucidate the role of hepatic stellate cells (HSCs) in the fibrotic process induced by E. multilocularis.
- To provide insights into the pathogenesis of liver fibrogenesis and inform treatment approaches for alveolar echinococcosis.
Main Methods:
- In vitro exposure of HSC-T6 and LX-2 cells to sera and parasite components (germinal cells, protoscoleces) from E. multilocularis-infected gerbils.
- Measurement of cell proliferation using CCK-8 assay and quantification of collagen 1 (Col1) and α-smooth muscle actin (α-SMA) levels via ELISA.
- Longitudinal analysis of serum Col1 and α-SMA concentrations and liver collagen deposition (Sirius red staining) in infected mice over 8 months.
Main Results:
- Sera and parasite components from E. multilocularis-infected gerbils significantly promoted HSC proliferation in vitro.
- Exposure to infected sera and parasite components led to increased Col1 and α-SMA levels in HSC culture supernatants.
- Persistent E. multilocularis infection in mice resulted in elevated serum Col1 and α-SMA levels and significant collagen fiber deposition in the liver, peaking at 6-8 months post-infection.
Conclusions:
- Persistent Echinococcus multilocularis infections stimulate hepatic stellate cell proliferation and induce key markers of liver fibrosis (Col1 and α-SMA).
- The study demonstrates a direct link between E. multilocularis infection and the development of hepatic fibrosis.
- The infective stage of E. multilocularis is identified as a critical period for the induction of hepatic fibrosis in alveolar echinococcosis.
