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Brief Research Report ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00190

In chronic hepatitis C infection, myeloid-derived suppressor cell accumulation and T cell dysfunctions revert partially and late after successful direct-acting antiviral treatment

Valentina Telatin1,  Francesco Nicoli1, Chiara Frasson2, Nicola Menegotto1, Francesco Barbaro3,  Eleonora Castelli3, Elke Erne3,  Giorgio Palù1 and  Antonella Caputo1*
  • 1Department of Molecular Medicine, School of Medicine and Surgery, University of Padova, Italy
  • 2Istituto di Ricerca Pediatrica, Fondazione Città della Speranza, Italy
  • 3Unit of Infectious and Tropical Diseases, University Hospital of Padua, Italy

Chronic HCV infection is characterized by several immunological alterations, such as the accumulation of suppressor cells and of hyperactivated T lymphocytes. However, it is unclear whether direct-acting antiviral (DAA)-mediated HCV clearance restores immune dysfunctions. We performed a phenotypic characterization by flow cytometry of different immune cell subsets, including monocytic myeloid-derived suppressor cells (M-MDSCs) and T lymphocytes in 168 patients with persistent HCV infection not treated, under DAA therapies and sustained virological responders. Chronic HCV infection prompted the accumulation of M-MDSCs independently of patient and clinical characteristics, and altered their metabolic properties. HCV RNA was undetectable in the majority of patients just after few weeks of DAA therapy, whereas M-MDSC levels normalized only 6 months after therapy. In addition, HCV infection deeply perturbed the T cell compartment since a re-distribution of memory CD4+ and CD8+ T cells was observed at the expenses of naïve cells, and memory T lymphocytes displayed increased activation. Notably, these features were only partially restored by DAA therapies in the CD4, but not in the CD8, compartment as high immune activation levels persisted in the terminally differentiated memory CD8+ T cells even more than one year after sustained virological response. Together, these results suggest that successful DAA therapies do not lead to full immunological reconstitution as fast as viral clearance.

Keywords: HCV, hepatitis C virus, DAA, M-MDS, monocytic MDSC, Treg - regulatory T cell, T lymophocytes

Received: 01 Mar 2019; Accepted: 17 May 2019.

Edited by:

Margarita Sáiz, Severo Ochoa Molecular Biology Center (CSIC-UAM), Spain

Reviewed by:

Raphael Gaudin, UMR9004 Institut de Recherche en Infectiologie de Montpellier (IRIM), France
Santosh Dhakal, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, United States  

Copyright: © 2019 Telatin, Nicoli, Frasson, Menegotto, Barbaro, Castelli, Erne, Palù and Caputo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Antonella Caputo, Department of Molecular Medicine, School of Medicine and Surgery, University of Padova, Padova, Italy,