Natural killer cells in hepatitis B virus infection

Wu, Shao-Fei; Wang, Wenjing; Gao, Yueqiu

doi:10.1016/j.bjid.2015.05.006

Cited by 22 publications

(12 citation statements)

References 81 publications

(119 reference statements)

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“…NK cells play an essential role in liver immunity and act as the first line of defense against invading pathogens. They generally become activated and eliminate HBV-infected cells directly by cytolytic killing and indirectly by secreting cytokines ( 32 , 33 ). Nevertheless, the frequency, activation, and cytokine production by circulating NK cells were significantly reduced in patients with HBV infection ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Lower Expression of MicroRNA-155 Contributes to Dysfunction of Natural Killer Cells in Patients with Chronic Hepatitis B

Huang

Liu

et al. 2017

Front. Immunol.

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MicroRNAs have been reported to be regulated in different ways in a variety of liver diseases. As a key modulator of cellular function in both innate and adaptive immunity, the role of miR-155 in chronic hepatitis B virus infection remains largely unknown. Here, we investigated the expression and function of miR-155 in chronic hepatitis B (CHB) patients. It was found that miR-155 expression in peripheral blood mononuclear cells (PBMCs) was lower in CHB patients than healthy controls (HC). Among CHB infection, immune-active (IA) patients with abnormal alanine aminotransferase (ALT) levels had relatively higher miR-155 expression in PBMCs and serum than immune-tolerant carriers, but were comparable to inactive carriers. Moreover, there was a positive correlation between miR-155 expression and ALT levels in CHB patients. Particularly, miR-155 expression in natural killer (NK) cells was significantly downregulated in IA patients compared with HC. Inversely, suppressor of cytokine signaling 1 (SOCS1), a target of miR-155, was upregulated in NK cells of IA patients. Overexpression of miR-155 in NK cells from IA patients led to a decrease in SOCS1 expression and an increase of IFN-γ production. Finally, accompanied by the normalization of ALT, miR-155 expression in PBMCs gradually decreased during telbivudine or peg-IFN-α-2a therapy. Interestingly, higher miR-155 expression at baseline was associated with better response to telbivudine therapy, but not peg-IFN-α-2a. In conclusion, our data suggested that miR-155 downregulation in NK cells of IA patients impaired IFN-γ production by targeting SOCS1, which may contribute to immune dysfunction during CHB infection. Additionally, baseline miR-155 expression could predict the treatment response to telbivudine therapy.

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Section: Discussionmentioning

confidence: 99%

Lower Expression of MicroRNA-155 Contributes to Dysfunction of Natural Killer Cells in Patients with Chronic Hepatitis B

Huang

Liu

et al. 2017

Front. Immunol.

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“…Among the main predisposing risk factors of HCC, there are chronic HBV and HCV infections [ 160 ]. In the acute phase of HCV and HBV infection, the NK cells display increased IFN-γ production and increased cytotoxicity, although, the specific contribution of NK cells to antiviral response is still unknown [ 161 , 162 ]. During this period, HCV patients are typically clinically asymptomatic and, without treatment, two-thirds of the infected patients develop chronic disease.…”

Section: Nk–dc Crosstalk In Primary Liver Cancermentioning

confidence: 99%

Natural Killer–Dendritic Cell Interactions in Liver Cancer: Implications for Immunotherapy

Cazzetta

Franzese

Carenza

et al. 2021

Cancers

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Natural killer (NK) and dendritic cells (DCs) are innate immune cells that play a crucial role in anti-tumor immunity. NK cells kill tumor cells through direct cytotoxicity and cytokine secretion. DCs are needed for the activation of adaptive immune responses against tumor cells. Both NK cells and DCs are subdivided in several subsets endowed with specialized effector functions. Crosstalk between NK cells and DCs leads to the reciprocal control of their activation and polarization of immune responses. In this review, we describe the role of NK cells and DCs in liver cancer, focusing on the mechanisms involved in their reciprocal control and activation. In this context, intrahepatic NK cells and DCs present unique immunological features, due to the constant exposure to non-self-circulating antigens. These interactions might play a fundamental role in the pathology of primary liver cancer, namely hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Additionally, the implications of these immune changes are relevant from the perspective of improving the cancer immunotherapy strategies in HCC and ICC patients.

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“…In both the early immune responses and the chronic phase, these types of cells contribute to HBV infection. Wu et al ( 21 ) reviewed the role of NK cells in HBV infection, discussing the mechanisms of action of this arm of the innate immune system in HBV infection.…”

Section: Immune System Response and Hepatitis B Virus Infectionmentioning

confidence: 99%

Hepatitis B Reactivation During Immunosuppressive Therapy or Cancer Chemotherapy, Management, and Prevention: A Comprehensive Review

2016

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ContextDue to the close relationship between the immune system and the hepatitis B virus (HBV) replication, it is essential to monitor patients with current or past HBV infection under any type of immunosuppression. Cancer chemotherapy, immunosuppressive therapies in autoimmune diseases, and immunosuppression in solid organ and stem cell transplant recipients are the major reasons for hepatitis B virus reactivation (HBVr). In this review, the challenges associated with HBVr are discussed according to the latest studies and guidelines. We also discuss the role of treatments with different risks, including anti-CD20 agents, tumor necrosis factor-alpha (TNF-α) inhibitors, and other common immunosuppressive agents in various conditions.Evidence AcquisitionThrough an electronic search of the PubMed, Google Scholar, and Scopus databases, we selected the studies associated with HBVr in different conditions. The most recent recommendations were collected in order to reach a consensus on how to manage patients at risk of HBVr.ResultsIt was found that the positive hepatitis B surface antigen (HBsAg), the high baseline HBV DNA level, the positive hepatitis B virus e antigen (HBeAg), and an absent or low hepatitis B surface antibody (HBsAb) titer prior to starting treatment are the most important viral risk factors. Furthermore, rituximab, anthracycline, and different types of TNF-α inhibitors were identified as the high-risk therapies. By analyzing the efficiency of prophylaxis on the prevention of HBVr, it was concluded that those with a high risk of antiviral resistance should not be used in long-term immunosuppressants. Receiving HBV antiviral agents at the commencement of immunosuppressant therapy or chemotherapy was demonstrated to be effective in decreasing the risk of HBVr. Prophylaxis could also be initiated before the start of therapy. For most immune suppressive regimes, antiviral therapy should be kept up for at least 6 months after the cessation of immunosuppressive drugs. However, the optimal time of prophylaxis keeping should be increased in cases associated with rituximab or hematopoietic stem cell transplants. According to the latest studies and guidelines from different bodies, recommendations regarding screening, monitoring, and management of HBVr are outlined.ConclusionsIdentification of patients at the risk of HBVr before immunosuppressive therapy is an undeniable part of treatment. Starting the antiviral therapy, based on the type of immunosuppressive drugs and the underlying disease, could lead to better management of disease.

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Natural killer cells in hepatitis B virus infection

Cited by 22 publications

References 81 publications

Lower Expression of MicroRNA-155 Contributes to Dysfunction of Natural Killer Cells in Patients with Chronic Hepatitis B

Lower Expression of MicroRNA-155 Contributes to Dysfunction of Natural Killer Cells in Patients with Chronic Hepatitis B

Natural Killer–Dendritic Cell Interactions in Liver Cancer: Implications for Immunotherapy

Hepatitis B Reactivation During Immunosuppressive Therapy or Cancer Chemotherapy, Management, and Prevention: A Comprehensive Review

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