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Impact of IFN-Free and IFN-Based Treatment on Blood Myeloid Dendritic Cell, Monocyte, Slan-DC, and Activated T Lymphocyte Dynamics during HCV Infection.

ABSTRACT: Chronic hepatitis C virus infection leads to the activation of innate immunity, a key component in HCV fibrosis. In the past, the use of IFN-based treatment regimens did not permit an adequate evaluation of the impact of HCV clearance on immune cells, because of their antiviral and immunomodulatory properties. The recent development of direct-acting antiviral (DAA) therapy, which is associated with high rates of sustained virological response, enables a more accurate analysis of the immunological modifications following HCV eradication. We studied the dynamics of blood myeloid dendritic cells, monocytes, slan-DCs, and T lymphocytes during IFN-free and IFN-based regimens in hepatitis C virus infection.

SUBMITTER: Vita S

PROVIDER: S-EPMC7102477 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Impact of IFN-Free and IFN-Based Treatment on Blood Myeloid Dendritic Cell, Monocyte, Slan-DC, and Activated T Lymphocyte Dynamics during HCV Infection.

Vita Serena S Zuccalà Paola P Savinelli Stefano S Mascia Claudia C Rossi Raffaella R Schiavone Francesco F Marocco Raffaella R Tieghi Tiziana T Iannetta Marco M Nijhawan Parni P Zingaropoli Maria Antonella MA d'Ettore Gabriella G Vullo Vincenzo V Mastroianni Claudio Maria CM Lichtner Miriam M

Journal of immunology research 20200316

Chronic hepatitis C virus infection leads to the activation of innate immunity, a key component in HCV fibrosis. In the past, the use of IFN-based treatment regimens did not permit an adequate evaluation of the impact of HCV clearance on immune cells, because of their antiviral and immunomodulatory properties. The recent development of direct-acting antiviral (DAA) therapy, which is associated with high rates of sustained virological response, enables a more accurate analysis of the immunologica ...[more]

PMID: 32258171

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Project description:BACKGROUND: Interferons alpha (IFN?) are the cytokines most widely used in clinical medicine for the treatment of cancer and viral infections. Among the immunomodulatory activities possibly involved in their therapeutic efficacy, the importance of IFN? effects on dendritic cells (DC) differentiation and activation has been considered. Despite several studies exploiting microarray technology to characterize IFN? mechanisms of action, there is currently no consensus on the core signature of these cytokines in the peripheral blood of IFN?-treated individuals, as well as on the existence of blood genomic and proteomic markers of low-dose IFN? administered as a vaccine adjuvant. METHODS: Gene profiling analysis with microarray was performed on PBMC isolated from melanoma patients and healthy individuals 24 hours after each repeated injection of low-dose IFN?, administered as vaccine adjuvant in two separate clinical trials. At the same time points, cytofluorimetric analysis was performed on CD14+ monocytes, to detect the phenotypic modifications exerted by IFN? on antigen presenting cells precursors. RESULTS: An IFN? signature was consistently observed in both clinical settings 24 hours after each repeated administration of the cytokine. The observed modulation was transient, and did not reach a steady state level refractory to further stimulations. The molecular signature observed ex vivo largely matched the one detected in CD14+ monocytes exposed in vitro to IFN?, including the induction of CXCL10 at the transcriptional and protein level. Interestingly, IFN? ex vivo signature was paralleled by an increase in the percentage and expression of costimulatory molecules by circulating CD14+/CD16+ monocytes, indicated as natural precursors of DC in response to danger signals. CONCLUSIONS: Our results provide new insights into the identification of a well defined molecular signature as biomarker of IFN? administered as immune adjuvants, and for the characterization of new molecular and cellular players, such as CXCL10 and CD14+/CD16+ cells, mediating and possibly predicting patient response to these cytokines.

Project description:HIV-2 infection is characterized by low viremia and slow disease progression as compared to HIV-1 infection. Circulating CD14++CD16+ monocytes were found to accumulate and CD11c+ conventional dendritic cells (cDC) to be depleted in a Portuguese cohort of people living with HIV-2 (PLWHIV-2), compared to blood bank healthy donors (HD). We studied more precisely classical monocytes; CD16+ inflammatory (intermediate, non-classical and slan+ monocytes, known to accumulate during viremic HIV-1 infection); cDC1, important for cross-presentation, and cDC2, both depleted during HIV-1 infection. We analyzed by flow cytometry these PBMC subsets from Paris area residents: 29 asymptomatic, untreated PLWHIV-2 from the IMMUNOVIR-2 study, part of the ANRS-CO5 HIV-2 cohort: 19 long-term non-progressors (LTNP; infection ≥8 years, undetectable viral load, stable CD4 counts≥500/μL; 17 of West-African origin -WA), and 10 non-LTNP (P; progressive infection; 9 WA); and 30 age-and sex-matched controls: 16 blood bank HD with unknown geographical origin, and 10 HD of WA origin (GeoHD). We measured plasma bacterial translocation markers by ELISA. Non-classical monocyte counts were higher in GeoHD than in HD (54 vs. 32 cells/μL, p = 0.0002). Slan+ monocyte counts were twice as high in GeoHD than in HD (WA: 28 vs. 13 cells/μL, p = 0.0002). Thus cell counts were compared only between participants of WA origin. They were similar in LTNP, P and GeoHD, indicating that there were no HIV-2 related differences. cDC counts did not show major differences between the groups. Interestingly, inflammatory monocyte counts correlated with plasma sCD14 and LBP only in PLWHIV-2, especially LTNP, and not in GeoHD. In conclusion, in LTNP PLWHIV-2, inflammatory monocyte counts correlated with LBP or sCD14 plasma levels, indicating a potential innate immune response to subclinical bacterial translocation. As GeoHD had higher inflammatory monocyte counts than HD, our data also show that specific controls are important to refine innate immunity studies.

Dataset Information

Impact of IFN-Free and IFN-Based Treatment on Blood Myeloid Dendritic Cell, Monocyte, Slan-DC, and Activated T Lymphocyte Dynamics during HCV Infection.

Publications

Impact of IFN-Free and IFN-Based Treatment on Blood Myeloid Dendritic Cell, Monocyte, Slan-DC, and Activated T Lymphocyte Dynamics during HCV Infection.

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