The immunological function of extracellular vesicles in hepatitis B virus-infected hepatocytes

Kakizaki, Masatoshi; Yamamoto, Yuichiro; Yabuta, Suemi; Kurosaki, Natsumi; Kagawa, Tatehiro; Kotani, Ai

doi:10.1371/journal.pone.0205886

Cited by 47 publications

(54 citation statements)

References 32 publications

(30 reference statements)

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“…In our cohort, beside the low levels of HLA-DR on monocytes and DCs, we also found higher levels of the suppressive molecule PD-L1, with only slightly higher levels of proinflammatory cytokines (IL-6, IL-1β, and TNFα) expression. The alteration of the PD-1/PD-L1 axis in chronic viral infections, such as hepatitis B or human immunodeficiency virus, has been well described [ 39 , 40 ]. For instance, the expression of PD-1 and PD-L1 was shown to be upregulated in monocytes and DCs in a STAT3-dependent manner in response to virus-induced production of IL-10 [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Disharmonic Inflammatory Signatures in COVID-19: Augmented Neutrophils’ but Impaired Monocytes’ and Dendritic Cells’ Responsiveness

Paračková

Zentsová

Bloomfield

et al. 2020

Cells

122

145

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COVID-19, caused by SARS-CoV-2 virus, emerged as a pandemic disease posing a severe threat to global health. To date, sporadic studies have demonstrated that innate immune mechanisms, specifically neutrophilia, NETosis, and neutrophil-associated cytokine responses, are involved in COVID-19 pathogenesis; however, our understanding of the exact nature of this aspect of host–pathogen interaction is limited. Here, we present a detailed dissection of the features and functional profiles of neutrophils, dendritic cells, and monocytes in COVID-19. We portray the crucial role of neutrophils as drivers of hyperinflammation associated with COVID-19 disease via the shift towards their immature forms, enhanced degranulation, cytokine production, and augmented interferon responses. We demonstrate the impaired functionality of COVID-19 dendritic cells and monocytes, particularly their low expression of maturation markers, increased PD-L1 levels, and their inability to upregulate phenotype upon stimulation. In summary, our work highlights important data that prompt further research, as therapeutic targeting of neutrophils and their associated products may hold the potential to reduce the severity of COVID-19.

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Section: Discussionmentioning

confidence: 99%

Disharmonic Inflammatory Signatures in COVID-19: Augmented Neutrophils’ but Impaired Monocytes’ and Dendritic Cells’ Responsiveness

Paračková

Zentsová

Bloomfield

et al. 2020

Cells

122

145

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“…EVs play a particular role in viral hepatitis, as these vesicles can transport viral particles, overall enabling the expansion of the viral infection to surrounding cells [172,173]. Specifically, EVs are important for HBV-infected hepatocytes [174]. The production of EVs carrying HBV DNA from HBV-infected hepatocytes has been reported to depend on the ASMase/ceramide system to mediate exosome formation [175], indicating that the regulation of this pathway could be an important therapeutic approach to preventing EV-mediated HBV infection.…”

Section: Viral Hepatitis B (Hbv)mentioning

confidence: 99%

Sphingomyelinases and Liver Diseases

et al. 2020

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Sphingolipids (SLs) are critical components of membrane bilayers that play a crucial role in their physico-chemical properties. Ceramide is the prototype and most studied SL due to its role as a second messenger in the regulation of multiple signaling pathways and cellular processes. Ceramide is a heterogeneous lipid entity determined by the length of the fatty acyl chain linked to its carbon backbone sphingosine, which can be generated either by de novo synthesis from serine and palmitoyl-CoA in the endoplasmic reticulum or via sphingomyelin (SM) hydrolysis by sphingomyelinases (SMases). Unlike de novo synthesis, SMase-induced SM hydrolysis represents a rapid and transient mechanism of ceramide generation in specific intracellular sites that accounts for the diverse biological effects of ceramide. Several SMases have been described at the molecular level, which exhibit different pH requirements for activity: neutral, acid or alkaline. Among the SMases, the neutral (NSMase) and acid (ASMase) are the best characterized for their contribution to signaling pathways and role in diverse pathologies, including liver diseases. As part of a Special Issue (Phospholipases: From Structure to Biological Function), the present invited review summarizes the physiological functions of NSMase and ASMase and their role in chronic and metabolic liver diseases, of which the most relevant is nonalcoholic steatohepatitis and its progression to hepatocellular carcinoma, due to the association with the obesity and type 2 diabetes epidemic. A better understanding of the regulation and role of SMases in liver pathology may offer the opportunity for novel treatments of liver diseases.

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“…These EV could act as an antibody bait during HCV infection. Kakizaki et al demonstrated in vitro that replicating hepatitis B virus (HBV)‐infected hepatocytes (HepAD38) produced EV that were able to induce monocyte upregulation of programmed death ligand‐1 which can induce immune suppression of T cells . This effect was enhanced when infected hepatocytes were treated with the nucleotide reverse transcriptase inhibitor tenofovir and was associated with an increase of supernatant pregenomic RNA suggesting its role in immune suppression of monocytes.…”

Section: Extracellular Vesicles In Chronic Liver Diseasesmentioning

confidence: 99%

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration

Balaphas

Meyer

Sadoul

et al. 2019

Liver International

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Extracellular vesicles are membrane fragments that can be produced by all cell types. Interactions between extracellular vesicles and various liver cells constitute an emerging field in hepatology and recent evidences have established a role for extracellular vesicles in various liver diseases and physiological processes. Extracellular vesicles originating from liver cells are implicated in intercellular communication and fluctuations of specific circulating extracellular vesicles could constitute new diagnostic tools. In contrast, extracellular vesicles derived from progenitor cells interact with hepatocytes or non‐parenchymal cells, thereby protecting the liver from various injuries and promoting liver regeneration. Our review focuses on recent developments investigating the role of various types of extracellular vesicles in acute and chronic liver diseases as well as their potential use as biomarkers and therapeutic tools.

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The immunological function of extracellular vesicles in hepatitis B virus-infected hepatocytes

Cited by 47 publications

References 32 publications

Disharmonic Inflammatory Signatures in COVID-19: Augmented Neutrophils’ but Impaired Monocytes’ and Dendritic Cells’ Responsiveness

Disharmonic Inflammatory Signatures in COVID-19: Augmented Neutrophils’ but Impaired Monocytes’ and Dendritic Cells’ Responsiveness

Sphingomyelinases and Liver Diseases

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration

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