HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients’ clinical stage
Background:. Hepatitis B is a liver infection caused by HBV. Infected individuals who fail to control the viral infection develop chronic hepatitis B and are at risk of developing life-threatening liver diseases, such as cirrhosis or liver cancer. Dendritic cells (DCs) play important roles in the im...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Health/LWW
2025-02-01
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| Series: | Hepatology Communications |
| Online Access: | http://journals.lww.com/10.1097/HC9.0000000000000625 |
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| author | Lucile Dumolard Theophile Gerster Florent Chuffart Thomas Decaens Marie-Noelle Hilleret Sylvie Larrat Philippe Saas Evelyne Jouvin-Marche David Durantel Patrice N. Marche Zuzana Macek Jilkova Caroline Aspord |
| author_facet | Lucile Dumolard Theophile Gerster Florent Chuffart Thomas Decaens Marie-Noelle Hilleret Sylvie Larrat Philippe Saas Evelyne Jouvin-Marche David Durantel Patrice N. Marche Zuzana Macek Jilkova Caroline Aspord |
| author_sort | Lucile Dumolard |
| collection | DOAJ |
| description | Background:. Hepatitis B is a liver infection caused by HBV. Infected individuals who fail to control the viral infection develop chronic hepatitis B and are at risk of developing life-threatening liver diseases, such as cirrhosis or liver cancer. Dendritic cells (DCs) play important roles in the immune response against HBV but are functionally impaired in patients with chronic hepatitis B. The underlying mechanisms involved in HBV-induced DC dysfunctions remain to be elucidated.
Methods:. We explored DC modulations by HBV and HBsAg by exposing blood-derived cDC1s, cDC2s, and plasmacytoid DCs from healthy donors to HBV or HBsAg and stimulating them with toll-like receptor ligand. Their phenotypic and functional features, as well as their metabolic profile, were analyzed through multiparametric flow cytometry and multiplex assays and further explored on patients’ samples.
Results:. We found that HBV deeply reshaped the DC secretome in response to toll-like receptor ligand. Strikingly, we observed that HBV-exposed DCs secrete high levels of CX3CL1 (fractalkine), a chemokine responsible for attracting antiviral effectors to the site of infection. HBsAg exposure favored DC activation while drastically altering TRAIL expression in response to toll-like receptor ligand and increasing the secretion of cytokines/chemokines involved in immune tolerance. HBsAg further dampened the metabolism of DC subsets while driving metabolic switches. Notably, the relevance of the CX3CL1/CX3CR1 axis, TGF-β, and metabolic disturbances was demonstrated within intrahepatic DC subsets in patients according to disease stage.
Conclusions:. Our work brings new insights into the immunomodulation induced by HBV on DCs, which contribute to impaired antiviral responses and progression toward chronicity. |
| format | Article |
| id | doaj-art-5d6f452019da4a4fbd33ef404d584b67 |
| institution | Kabale University |
| issn | 2471-254X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj-art-5d6f452019da4a4fbd33ef404d584b672025-02-05T02:10:59ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2025-02-019210.1097/HC9.0000000000000625HC90000000000000625HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients’ clinical stageLucile Dumolard0Theophile Gerster1Florent Chuffart2Thomas Decaens3Marie-Noelle Hilleret4Sylvie Larrat5Philippe Saas6Evelyne Jouvin-Marche7David Durantel8Patrice N. Marche9Zuzana Macek Jilkova10Caroline Aspord11 1 University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France 2 Hepato-Gastroenterology and Digestive Oncology Department, CHU Grenoble Alpes, Grenoble, France 1 University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France 1 University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France 1 University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France 4 University Grenoble Alpes, Laboratoire de Virologie, CHU Grenoble Alpes, Grenoble, France 1 University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France 1 University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France 5 INSERM, U1111, Centre International de Recherche en Infectiologie (CIRI), University of Lyon (UCBL1), CNRS UMR_5308, ENS de Lyon, Lyon, France 1 University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France 1 University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France 1 University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, FranceBackground:. Hepatitis B is a liver infection caused by HBV. Infected individuals who fail to control the viral infection develop chronic hepatitis B and are at risk of developing life-threatening liver diseases, such as cirrhosis or liver cancer. Dendritic cells (DCs) play important roles in the immune response against HBV but are functionally impaired in patients with chronic hepatitis B. The underlying mechanisms involved in HBV-induced DC dysfunctions remain to be elucidated. Methods:. We explored DC modulations by HBV and HBsAg by exposing blood-derived cDC1s, cDC2s, and plasmacytoid DCs from healthy donors to HBV or HBsAg and stimulating them with toll-like receptor ligand. Their phenotypic and functional features, as well as their metabolic profile, were analyzed through multiparametric flow cytometry and multiplex assays and further explored on patients’ samples. Results:. We found that HBV deeply reshaped the DC secretome in response to toll-like receptor ligand. Strikingly, we observed that HBV-exposed DCs secrete high levels of CX3CL1 (fractalkine), a chemokine responsible for attracting antiviral effectors to the site of infection. HBsAg exposure favored DC activation while drastically altering TRAIL expression in response to toll-like receptor ligand and increasing the secretion of cytokines/chemokines involved in immune tolerance. HBsAg further dampened the metabolism of DC subsets while driving metabolic switches. Notably, the relevance of the CX3CL1/CX3CR1 axis, TGF-β, and metabolic disturbances was demonstrated within intrahepatic DC subsets in patients according to disease stage. Conclusions:. Our work brings new insights into the immunomodulation induced by HBV on DCs, which contribute to impaired antiviral responses and progression toward chronicity.http://journals.lww.com/10.1097/HC9.0000000000000625 |
| spellingShingle | Lucile Dumolard Theophile Gerster Florent Chuffart Thomas Decaens Marie-Noelle Hilleret Sylvie Larrat Philippe Saas Evelyne Jouvin-Marche David Durantel Patrice N. Marche Zuzana Macek Jilkova Caroline Aspord HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients’ clinical stage Hepatology Communications |
| title | HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients’ clinical stage |
| title_full | HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients’ clinical stage |
| title_fullStr | HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients’ clinical stage |
| title_full_unstemmed | HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients’ clinical stage |
| title_short | HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients’ clinical stage |
| title_sort | hbv and hbsag strongly reshape the phenotype function and metabolism of dcs according to patients clinical stage |
| url | http://journals.lww.com/10.1097/HC9.0000000000000625 |
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