scholarly journals High L-Carnitine Levels Impede Viral Control in Chronic Hepatitis B Virus Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuqin Gu ◽  
Xin Fu ◽  
Guofu Ye ◽  
Chengcong Chen ◽  
Xiaoyi Li ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
Immune Responses ◽  
Immune Cells ◽  
Hbv Infection ◽  
Viral Control ◽  
Chronic Hbv Infection ◽  
Hbsag Loss ◽  
Chronic Hbv

Persistent antigen exposure during chronic hepatitis B infection leads to exhausted immune responses, thus impeding viral control. In recent years, immunometabolism opens new therapeutic possibilities for the modulation of immune responses. Herein, we investigated the immunomodulatory effect of L-carnitine (L-Cn) on immune cells in chronic HBV infection. In this study, 141 treatment-naïve patients with chronic HBV infection, 38 patients who achieved HBsAg loss following antiviral treatment, and 47 patients who suffered from HBV-related HCC from real-life clinical practice were recruited. The plasma L-Cn levels were measured by ELISA. RNA sequencing was conducted to define the transcriptional profiles of peripheral blood mononuclear cells after L-Cn stimulation. In vitro assays were performed to assess the effect of L-Cn on immune cells; the frequencies and function of immune cells were analyzed by flow cytometry. We found that compared with patients with HBsAg loss, patients with HBsAg positivity and patients who suffered from HBV-related HCC had higher levels of L-Cn, and the plasma levels of L-Cn in the HBeAg-positive chronic hepatitis patients who had elevated ALT were significantly higher than that of HBeAg-negative chronic infection and HBsAg loss groups. Moreover, a positive correlation between plasma levels of L-Cn and HBsAg levels was found. Additionally, RNA sequencing analysis demonstrated that L-Cn altered the transcriptional profiles related to immune response. In vitro assays revealed that L-Cn suppressed the proliferation of and IFN-γ production by CD4+ and CD8+ T cells. It also down-regulated the proliferation and IgG production of B cells. Notably, L-Cn enhanced IL-10 secretion from regulatory T cells and up-regulated the expression of inhibitory receptors on T cells. Moreover, a variant in CPT2 (rs1799821) was confirmed to be associated with L-Cn levels as well as complete response in CHB patients following Peg-IFNα antiviral therapy. Taken together, the immunosuppressive properties of L-Cn may hinder the control of HBV in chronic HBV infection, implicating that L-Cn manipulation might influence the prognosis of patients with HBV infection.

scholarly journals CXCL13-mediated recruitment of intrahepatic CXCR5+CD8+ T cells favors viral control in chronic HBV infection

2020 ◽  
Vol 72 (3) ◽  
pp. 420-430 ◽  
Author(s):  
Yongyin Li ◽  
Libo Tang ◽  
Ling Guo ◽  
Chengcong Chen ◽  
Shuqin Gu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Hbv Infection ◽  
Viral Control ◽  
Chronic Hbv Infection ◽  
Chronic Hbv

scholarly journals Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

2020 ◽  
Author(s):  
Xiaoyi Li ◽  
Qifan Zhang ◽  
Wanyue Zhang ◽  
Guofu Ye ◽  
Yanchen Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Hbv Infection ◽  
Follicular Dendritic Cells ◽  
Chronic Hbv Infection ◽  
Chronic Hbv

Abstract Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4 + T cells and CD19 + B cells.Results: We found that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared with that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, a positive correlation between the frequency of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5) + CD4 + T cells and CXCR5 + CD8 + T cells was also observed. Notably, in vitro experiments demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4 + T cells and promoted the proliferation of autologous intrasplenic CD19 + B cells. Conclusions: Expanded FDCs in patients with chronic HBV infection may favor the host immune responses against HBV. The identification of this unique population may contribute to a better understanding of the immune regulatory mechanisms and provide a potential immunotherapeutic target in chronic HBV infection.

T cell dysfunction in chronic hepatitis B infection and liver cancer: evidence from transcriptome analysis

2018 ◽  
Vol 56 (1) ◽  
pp. 22-28 ◽  
Author(s):  
Yu-Gang Wang ◽  
Dong-Hui Zheng ◽  
Min Shi ◽  
Xi-Ming Xu
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
T Cell ◽  
Virus Infection ◽  
Hbv Infection ◽  
Differentially Expressed ◽  
Chronic Hbv Infection ◽  
Cell Dysfunction ◽  
T Cell Dysfunction ◽  
Chronic Hbv

BackgroundT cell dysfunction occurs in many diseases, especially in chronic virus infection and cancers. However, up to now, little is known on the distinctions in T cell exhaustion between cancer and chronic virus infection. The objective of this study is to explore the transcriptional similarities and differences in exhausted CD8 +T cell between chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC).MethodsRNA sequencing was performed to compare the transcriptome of CD8 +T cells isolated from healthy donors’ blood, tumour tissues of patients with HCC and chronic HBV infected HCC patients’ paracancerous tissues. DESeq2 algorithm was used to determine differentially expressed genes. Gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted for in-depth analysis of these differentially expressed genes.ResultsA total number of 2109 and 2203 genes were differentially expressed in patients with chronic HBV infection and HCC, respectively. Comparing these two groups of differentially deregulated genes, we found that nearly half of them were shared, and these shared genes were further classified into several functional categories, such as metabolic process, binding and intracellular organelle. KEGG analysis revealed that these shared deregulated genes were involved in many important pathways such as Parkinson’s disease, oxidative phosphorylation and messenger RNA surveillance. Interestingly, we reported that chronic HBV infection specific deregulated genes were mainly enriched in graft versus host disease, allograft rejection, phenylalanine, tyrosine and tryptophan biosynthesis pathways. Whereas, HCC-specific deregulated genes were highly enriched in oxidative phosphorylation, thyroid cancer and endometrial cancer pathways.ConclusionOur study demonstrated that T cell dysfunction associated with HCC and chronic HBV infection shares high similarities, however, each possesses its own features in terms of specific genes and signalling pathways. Uncovering the differences of T cells dysfunction would facilitate our understanding the diseases pathogenesis and developing innovative therapies in the future.

scholarly journals Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaoyi Li ◽  
Qifan Zhang ◽  
Wanyue Zhang ◽  
Guofu Ye ◽  
Yanchen Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Hbv Infection ◽  
Follicular Dendritic Cells ◽  
Chronic Hbv Infection ◽  
Chronic Hbv ◽  
Follicular Dendritic

Abstract Background The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4+ T cells and CD19+ B cells. Results We observed that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared to that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, positive correlations were observed between the frequencies of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5)+CD4+ T cells and CXCR5+CD8+ T cells. Notably, in vitro experimental results demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4+ T cells and promoted the proliferation of autologous intrasplenic CD19+ B cells. Conclusions Expanded FDCs in patients with chronic HBV infection may favor host immune responses against HBV. The identification of this unique population of cell may contribute to a better understanding of the immune regulatory mechanisms associated with chronic HBV infection and provide a potential immunotherapeutic target for this disease.

scholarly journals Expanded Circulating Follicular Dendritic Cells Facilitate Immune Responses in Chronic HBV Infection

2020 ◽  
Author(s):  
Xiaoyi Li ◽  
Qifan Zhang ◽  
Wanyue Zhang ◽  
Guofu Ye ◽  
Yanchen Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Hbv Infection ◽  
Follicular Dendritic Cells ◽  
Chronic Hbv Infection ◽  
Chronic Hbv ◽  
Follicular Dendritic

Abstract Background: Restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. This study aims to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4+ T cells and CD19+ B cells. Results: We found that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared with that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, a positive correlation between the frequency of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5)+CD4+ T cells and CXCR5+CD8+ T cells was also observed. Notably, in vitro experiments demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4+ T cells and promoted the proliferation of autologous intrasplenic CD19+ B cells.Conclusions: Expanded FDCs in patients with chronic HBV infection may favor the host immune responses against HBV. The identification of this unique population may contribute to a better understanding of the immune regulatory mechanisms and provide a potential immunotherapeutic target in chronic HBV infection.

scholarly journals Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

2020 ◽  
Author(s):  
Xiaoyi Li ◽  
Qifan Zhang ◽  
Wanyue Zhang ◽  
Guofu Ye ◽  
Yanchen Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Hbv Infection ◽  
Follicular Dendritic Cells ◽  
Chronic Hbv Infection ◽  
Chronic Hbv ◽  
Follicular Dendritic

Abstract Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4+ T cells and CD19+ B cells. Results: We observed that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared to that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, positive correlations were observed between the frequencies of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5)+CD4+ T cells and CXCR5+CD8+ T cells. Notably, in vitro experimental results demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4+ T cells and promoted the proliferation of autologous intrasplenic CD19+ B cells.Conclusions: Expanded FDCs in patients with chronic HBV infection may favor host immune responses against HBV. The identification of this unique population of cell may contribute to a better understanding of the immune regulatory mechanisms associated with chronic HBV infection and provide a potential immunotherapeutic target for this disease.

Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection

Gut ◽  
2018 ◽  
Vol 68 (5) ◽  
pp. 893-904 ◽  
Author(s):  
Ruben C Hoogeveen ◽  
Maxwell P Robidoux ◽  
Tatjana Schwarz ◽  
Laura Heydmann ◽  
James A Cheney ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Infection ◽  
T Cell Response ◽  
Hbv Infection ◽  
Functional Cure ◽  
Viral Control ◽  
Chronic Hbv Infection ◽  
Chronic Hbv ◽  
And Function

ObjectiveChronic HBV infection affects more than 250 million people worldwide and remains a global healthcare problem in part because we lack curative treatment. Sustained viral control requires HBV-specific T cells, but these become functionally impaired in chronic infection. Clinical evidence indicates that functional cure of HBV infection by the host immune response is feasible. Developing T cell-based therapies able to achieve functional cure will require identification of the requirements for a successful T cell response against HBV and the relative contribution of individual T cell specificities to HBV control.DesignThe phenotype and function of HBV-specific T cells were studied directly ex vivo using fluorochrome-labelled multimers. We studied multiple HBV-specific T cell specificities targeting different HBV proteins in individuals with either an acute self-limiting or chronic HBV infection.ResultsWe detected strong T cell responses targeting multiple HBV viral proteins in acute self-limiting and low-frequency core and polymerase-specific T cells in chronic infection. Expression of the T cell inhibitory receptor PD-1, as well as T cell differentiation, T cell function and T cell regulation differed by stages and outcomes of infection. In addition, these features differed significantly between T cells targeting different HBV specificities.ConclusionHBV-specific T cells with different target specificities are characterised by distinct phenotypical and functional profiles. These results have direct implications for the design of immunological studies in HBV infection, and are potentially relevant for informing immunotherapeutic approaches to induce functional cure.

scholarly journals Increased CCR7loPD-1hiCXCR5+CD4+ T Cells in Peripheral Blood Mononuclear Cells Are Correlated with Immune Activation in Patients with Chronic HBV Infection

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Ya-Xin Huang ◽  
Qi-Yi Zhao ◽  
Li-Li Wu ◽  
Dong-Ying Xie ◽  
Zhi-Liang Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Antiviral Treatment ◽  
Hbv Infection ◽  
Peripheral Blood Mononuclear ◽  
Chronic Hbv Infection ◽  
Chronic Hepatitis B Virus ◽  
Chronic Hbv ◽  
Immune Tolerant

T follicular helper cells (Tfh cells) affect essential immune pathogenesis in chronic hepatitis B virus (HBV) infection. The CCR7loPD-1hi Tfh subset has a partial Tfh effector phenotype and is associated with active Tfh differentiation, whereas the CCR7hiPD-1lo Tfh subset is a resting phenotype. We recruited 20 healthy volunteers and 77 patients with chronic HBV infection, including those in the immune tolerant (IT) phase (n=19), immune clearance (IC) phase (n=20), low replicative (LR) phase (n=18), and reactivation (RA) phase (n=20). The expression of CD4, CXCR5, PD-1, and CCR7 was detected in T cells from peripheral blood by flow cytometry. The frequency of the CCR7loPD-1hi T subset was significantly higher in the patients than in the healthy controls (14.92±4.87% vs 12.23±2.95%, p=0.018). The frequency of this Tfh subset in the IC group (18.42%±3.08) was increased compared with the IT group (11.94±2.87%, p=0.001) and LR group (13.65±4.93%, p=0.031) and was higher in the RA group than in the IT group (16.03±5.37% vs 11.94±2.87%, p=0.030). We observed a weak positive correlation between the CCR7loPD-1hi Tfh subset population and the alanine transaminase (ALT) level (r=0.370, p=0.001). The CCR7loPD-1h Tfh subset in the chronic HBV-infected patients was elevated to various degrees among the different immune phases. CCR7loPD-1hiCXCR5+CD4+ T cells are correlated with the immune status of chronic HBV infection patients and may be developed as a potential indicator for antiviral treatment.

scholarly journals Burden and impacts of chronic hepatitis B infection in rural Senegal: study protocol of a cross-sectional survey in the area of Niakhar (AmBASS ANRS 12356)

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e030211 ◽  
Author(s):  
Marion Coste ◽  
Maëlle De Sèze ◽  
Aldiouma Diallo ◽  
Maria Patrizia Carrieri ◽  
Fabienne Marcellin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Hepatitis ◽  
Population Level ◽  
Clinic Visit ◽  
Hbv Infection ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Chronic Hbv Infection ◽  
Home Based ◽  
Chronic Hbv

IntroductionThough Senegal has one of the highest estimated prevalence rates of chronic hepatitis B virus (HBV) infection worldwide, epidemiological data in the general population are lacking and consequences of the infection remain undocumented. The ANRS-12356 AmBASS study aims at evaluating the health and socioeconomic burden of chronic HBV infection at the individual, household and population level. Its specific objectives are (1) to document the epidemiology of chronic HBV infection, including prevalence and risk factors; (2) to assess the acceptability of home-based testing and first clinic visit; (3) to investigate the repercussions of chronic HBV infection on living conditions; and (4) to estimate the public health impact of chronic HBV infection at the population level and the feasibility of a decentralised model of HBV test and treat.Methods and analysisThis multidisciplinary cross-sectional survey includes a twofold data collection: (1) home-based screening using dried blood spot (DBS) sampling and collection of sociodemographic, economic and behavioural data, and (2) additional clinical and biological data collection in chronic HBV carriers at the first clinic visit. The prevalence of chronic HBV infection will be estimated in the general population and in key subgroups. Risk factors for HBV acquisition in children will be explored using case-control analysis. HBV burden will be assessed through comparisons of health and economic outcomes between households affected by the disease versus non-affected households. Last, an economic evaluation will assess costs and health benefits of scaling-up HBV care.Ethics and disseminationThis study was approved by the Senegalese National Ethical Committee for Research in Health, and received authorisation from the Senegalese Ministry of Health and the French Commission on Information Technology and Liberties (Senegalese Protocol Number: SEN17/15). The study results will be presented in peer-review journals, international conferences and at a workshop with national stakeholders in order to contribute to the design of programmes to address the HBV pandemic.Trial registration numberNCT03215732; Pre-results.

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