Prospects for NK-based immunotherapy of chronic HBV infection

Jin, Xiaomeng; Bi, Jiacheng

doi:10.3389/fimmu.2022.1084109

Cited by 4 publications

(5 citation statements)

References 107 publications

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“…Chronic HBV infection is one of the main causes of liver cirrhosis worldwide. While rapid NK cell response is crucial in the early stages of an HBV infection [15], studies in chronically HBV-infected patients demonstrate exhausted NK cell function that contributes to impaired HBV clearance [16]. In peripheral blood, NK cells account for around 10% of all mononuclear cells [17]; however, the frequency within the liver can rise to 50% [15].…”

Section: Discussionmentioning

confidence: 99%

“…While rapid NK cell response is crucial in the early stages of an HBV infection [15], studies in chronically HBV-infected patients demonstrate exhausted NK cell function that contributes to impaired HBV clearance [16]. In peripheral blood, NK cells account for around 10% of all mononuclear cells [17]; however, the frequency within the liver can rise to 50% [15]. It is important to emphasize that a pronounced NK cell response, in addition to the early clearance of the virus, may contribute to significant liver damage if HBV infection persists [6,[18][19][20].…”

Section: Discussionmentioning

confidence: 99%

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Cytokine Response of Natural Killer Cells to Hepatitis B Virus Infection Depends on Monocyte Co-Stimulation

Kupke,

Brucker,

Wettengel

et al. 2024

Viruses

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Hepatitis B virus (HBV) is a major driver of chronic hepatic inflammation, which regularly leads to liver cirrhosis or hepatocellular carcinoma. Immediate innate immune cell response is crucial for the rapid clearance of the infection. Here, natural killer (NK) cells play a pivotal role in direct cytotoxicity and the secretion of antiviral cytokines as well as regulatory function. The aim of this study was to further elucidate NK cell responses triggered by an HBV infection. Therefore, we optimized HBV in vitro models that reliably stimulate NK cells using hepatocyte-like HepG2 cells expressing the Na+-taurocholate co-transporting polypeptide (NTCP) and HepaRG cells. Immune cells were acquired from healthy platelet donors. Initially, HepG2-NTCP cells demonstrated higher viral replication compared to HepaRG cells. Co-cultures with immune cells revealed increased production of interferon-γ and tumor necrosis factor-α by NK cells, which was no longer evident in isolated NK cells. Likewise, the depletion of monocytes and spatial separation from target cells led to the absence of the antiviral cytokine production of NK cells. Eventually, the combined co-culture of isolated NK cells and monocytes led to a sufficient cytokine response of NK cells, which was also apparent when communication between the two immune cell subpopulations was restricted to soluble factors. In summary, our study demonstrates antiviral cytokine production by NK cells in response to HBV+ HepG2-NTCP cells, which is dependent on monocyte bystander activation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cytokine Response of Natural Killer Cells to Hepatitis B Virus Infection Depends on Monocyte Co-Stimulation

Kupke,

Brucker,

Wettengel

et al. 2024

Viruses

View full text Add to dashboard Cite

show abstract

“…However, chronic HBV infection can lead to T-cell exhaustion and functional impairment (Table 1 ), allowing the virus to persist[ 76 ]. According to Jin and Bi[ 66 ], a microarray study shows that HBV significantly increases the expression of Bcl-2-like protein 11 in HBV-specific CD8+ T cells, pointing to a critical mechanism for CD8+ T cell depletion during CHB infection. Inhibitory receptors such as PD-1, CTLA-4, CD244 (2B4), Tim-3, and lymphocyte activation gene 3 are present on exhausted HBV-specific CD8+ T cells, and these receptors closely resemble the transcriptional patterns of CD8+ T cells[ 66 , 77 ].…”

Section: Possible Immunological Mechanisms Of Hbv Reactivationmentioning

confidence: 99%

Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies

Ma,

Yan,

et al. 2024

World J Gastroenterol

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Hepatitis B virus (HBV) reactivation is a clinically significant challenge in disease management. This review explores the immunological mechanisms underlying HBV reactivation, emphasizing disease progression and management. It delves into host immune responses and reactivation’s delicate balance, spanning innate and adaptive immunity. Viral factors’ disruption of this balance, as are interactions between viral antigens, immune cells, cytokine networks, and immune checkpoint pathways, are examined. Notably, the roles of T cells, natural killer cells, and antigen-presenting cells are discussed, highlighting their influence on disease progression. HBV reactivation’s impact on disease severity, hepatic flares, liver fibrosis progression, and hepatocellular carcinoma is detailed. Management strategies, including anti-viral and immunomodulatory approaches, are critically analyzed. The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation. In conclusion, this comprehensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation. With a dedicated focus on understanding its implications for disease progression and the prospects of efficient management strategies, this article contributes significantly to the knowledge base. The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches, ultimately enhancing disease management and elevating patient outcomes. The dynamic landscape of management strategies is critically scrutinized, spanning anti-viral and immunomodulatory approaches. The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

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“…NK cells are crucial antiviral and antitumor immune cells, capable of exerting direct cytotoxic effects without MHC restriction and antibody dependence. They can also secrete various cytokines to regulate the immune microenvironment and kill target cells [ 85 , 86 ]. As mentioned earlier, HBV can indirectly impair NK cell activation through the use of exosomes.…”

Section: Hbv Modifies Exosomes To Reshape the Host Immune Microenviro...mentioning

confidence: 99%

Exosomes target HBV-host interactions to remodel the hepatic immune microenvironment

Wu,

Niu,

Shi

2024

J Nanobiotechnol

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Chronic hepatitis B poses a significant global burden, modulating immune cells, leading to chronic inflammation and long-term damage. Due to its hepatotropism, the hepatitis B virus (HBV) cannot infect other cells. The mechanisms underlying the intercellular communication among different liver cells in HBV-infected individuals and the immune microenvironment imbalance remain elusive. Exosomes, as important intercellular communication and cargo transportation tools between HBV-infected hepatocytes and immune cells, have been shown to assist in HBV cargo transportation and regulate the immune microenvironment. However, the role of exosomes in hepatitis B has only gradually received attention in recent years. Minimal literature has systematically elaborated on the role of exosomes in reshaping the immune microenvironment of the liver. This review unfolds sequentially based on the biological processes of exosomes: exosomes’ biogenesis, release, transport, uptake by recipient cells, and their impact on recipient cells. We delineate how HBV influences the biogenesis of exosomes, utilizing exosomal covert transmission, and reshapes the hepatic immune microenvironment. And based on the characteristics and functions of exosomes, potential applications of exosomes in hepatitis B are summarized and predicted. Graphical Abstract

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Prospects for NK-based immunotherapy of chronic HBV infection

Cited by 4 publications

References 107 publications

Cytokine Response of Natural Killer Cells to Hepatitis B Virus Infection Depends on Monocyte Co-Stimulation

Cytokine Response of Natural Killer Cells to Hepatitis B Virus Infection Depends on Monocyte Co-Stimulation

Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies

Exosomes target HBV-host interactions to remodel the hepatic immune microenvironment

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