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Article

Successful Direct Acting Antiviral Therapy in Chronic Hepatitis C Normalizes IFNγ and IL2 Production in T Cells Together with TLR8 Expression and Functionality in Peripheral Blood Mononuclear Cells

1
Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain
2
Group of Clinical and Translational Research in Digestive Diseases (IDIVAL), 39008 Santander, Spain
3
Immunology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain
4
Transplant and Autoimmunity Group, Research Institute Marqués de Valdecilla (IDIVAL), 39008 Santander, Spain
5
Flow Cytometry and Cell Isolation Unit (IDIVAL), 39008 Santander, Spain
6
Molecular Biology Department, University of Cantabria, 39008 Santander, Spain
*
Authors to whom correspondence should be addressed.
These authors are both senior authors.
Academic Editors: Pietro Andreone and Stefano Brillanti
Received: 18 February 2021 / Revised: 20 March 2021 / Accepted: 5 April 2021 / Published: 7 April 2021
(This article belongs to the Special Issue Viral Hepatitis Treatment)
Chronic hepatitis C infection (HCV) activates a systemic cell-mediated immune response characterized by the production of IFNγ and an innate immune response addressed by the activation of TLR signaling. We aimed to investigate whether HCV eradication by direct acting antivirals (DAA) leads to a recovery in cell-mediated immune response and TLR expression and functionality. Blood samples were obtained in HCV infected patients before DAA treatment and at week +48 after the end of treatment. Results were compared to healthy controls. Cell surface expression of TLR8 was assessed on peripheral blood mononuclear cells (PBMCs) by flow cytometry. Freshly isolated PBMCs were cultured with specific TLR8 agonists and intracellular production of cytokines was determined by flow-cytometry after ex vivo TLR8 activation with ssRNA 40. Production of IFNγ, IL2 and IL17 was assessed by flow cytometry in T cells after polyclonal activation. Included were 50 HCV-infected patients and 15 controls. TLR8 expression in PBMCs was significantly increased before treatment and recovered normal levels at week +48. Production of IL1b, IL6 and TNFα dependent on the activation of TLR8 in PBMCs was also increased in patients before DAA treatment, with a significant reduction at week +48. Combined expression of IFNγ and IL2 in CD4+ T cells in HCV-infected patients was significantly increased compared to controls and recovered normal levels at week +48. DAA-mediated clearance of HCV is associated with a decreased expression and activation of TLR8 in PBMCs until healthy control levels which is accompanied by a reduction in the Th1 response. View Full-Text
Keywords: chronic hepatitis C; toll-like receptors; direct acting antivirals chronic hepatitis C; toll-like receptors; direct acting antivirals
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MDPI and ACS Style

Arias-Loste, M.T.; Cabezas, J.; Llerena, S.; Iruzubieta, P.; San-Segundo, D.; Merino, D.; Cuadrado, A.; Vaqué, J.P.; López-Hoyos, M.; Crespo, J. Successful Direct Acting Antiviral Therapy in Chronic Hepatitis C Normalizes IFNγ and IL2 Production in T Cells Together with TLR8 Expression and Functionality in Peripheral Blood Mononuclear Cells. Viruses 2021, 13, 635. https://0-doi-org.brum.beds.ac.uk/10.3390/v13040635

AMA Style

Arias-Loste MT, Cabezas J, Llerena S, Iruzubieta P, San-Segundo D, Merino D, Cuadrado A, Vaqué JP, López-Hoyos M, Crespo J. Successful Direct Acting Antiviral Therapy in Chronic Hepatitis C Normalizes IFNγ and IL2 Production in T Cells Together with TLR8 Expression and Functionality in Peripheral Blood Mononuclear Cells. Viruses. 2021; 13(4):635. https://0-doi-org.brum.beds.ac.uk/10.3390/v13040635

Chicago/Turabian Style

Arias-Loste, María T., Joaquín Cabezas, Susana Llerena, Paula Iruzubieta, David San-Segundo, David Merino, Antonio Cuadrado, José P. Vaqué, Marcos López-Hoyos, and Javier Crespo. 2021. "Successful Direct Acting Antiviral Therapy in Chronic Hepatitis C Normalizes IFNγ and IL2 Production in T Cells Together with TLR8 Expression and Functionality in Peripheral Blood Mononuclear Cells" Viruses 13, no. 4: 635. https://0-doi-org.brum.beds.ac.uk/10.3390/v13040635

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