Chronic hepatitis C infection–induced liver fibrogenesis is associated with M2 macrophage activation
Open accessAbstract
The immuno-pathogenic mechanisms of chronic hepatitis C virus (HCV) infection remain to be elucidated and pose a major hurdle in treating or preventing chronic HCV-induced advanced liver diseases such as cirrhosis. Macrophages are a major component of the inflammatory milieu in chronic HCV–induced liver disease, and are generally derived from circulating inflammatory monocytes; however very little is known about their role in liver diseases. To investigate the activation and role of macrophages in chronic HCV–induced liver fibrosis, we utilized a recently developed humanized mouse model with autologous human immune and liver cells, human liver and blood samples and cell culture models of monocyte/macrophage and/or hepatic stellate cell activation. We showed that M2 macrophage activation was associated with liver fibrosis during chronic HCV infection in the livers of both humanized mice and patients, and direct-acting antiviral therapy attenuated M2 macrophage activation and associated liver fibrosis. We demonstrated that supernatant from HCV-infected liver cells activated human monocytes/macrophages with M2-like phenotypes. Importantly, HCV-activated monocytes/macrophages promoted hepatic stellate cell activation. These results suggest a critical role for M2 macrophage induction in chronic HCV-associated immune dysregulation and liver fibrosis.
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In chronic viral hepatitis or parasitic infections, excessive anti-inflammatory polarization may impair pathogen clearance and perpetuate chronic inflammation.
“In these settings, excessive anti-inflammatory polarization may impair pathogen clearance and perpetuate chronic inflammation, thereby reshaping macrophage function (129–135).”
From Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages (2026) · cites this paper as [135]
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Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages
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- Authors
- Bility, M. T., Nio, K., Li, F., McGivern, D. R., Lemon, S. M., Feeney, E. R., Chung, R. T., & Su, L.
- Affiliations
- University of Pittsburgh (US)
- University of North Carolina at Chapel Hill (US)
- University College Dublin (IE)
- Harvard University (US)
- Corresponding author
- Bility, Moses T.
- Su, Lishan
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-12-21
- Volume
- 6
- Issue
- 1
- Pages
- 39520-39520
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5175173
- OpenAlex
- W2561815902
- Cited by
- 71
- References
- 1
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 5 · 2019: 12 · 2018: 10 · 2017: 6
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- UNC Libraries
- Funders
- Harvard University (5P30AI060354)
- National Institutes of Health (AI50410, DK098079)
- National Institute on Alcohol Abuse and Alcoholism (R21AA018009)
- National Cancer Institute (R01CA164029, P30CA016086)
- National Institute of Allergy and Infectious Diseases (R01AI095690, R01AI095097, R21AI076142, R21AI115207, P30AI050410, P30AI060354)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK098079, R01DK108370, R56DK098079)
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
- Center for AIDS Research, University of North Carolina at Chapel Hill (P30 AI‐50410)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- chronic hepatitis C, liver fibrosis, hepatic stellate cell activation, monocyte/macrophage activation, direct-acting antiviral therapy, humanized mice, liver cirrhosis, immune dysregulation
- MeSH terms
- Animals, Antiviral Agents, Chronic Disease, Disease Models, Animal, Humans, Immune System, Inflammation, Liver, Liver Cirrhosis, Macrophage Activation, Macrophages, Hepacivirus, Hepatitis C, Chronic, Mice, Hepatic Stellate Cells
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