Natural Killer‐Cell Cytotoxicity in HIV‐Positive and HIV‐Negative Patients with and Without Severe Course of Hepatitis B Virus Infection

Morsica, Giulia; Tasca, Silvana; Biswas, Priscilla; Galli, Andrea; Malnati, Mauro S.; Paties, Carlo; Marinelli, M; Bagaglio, Sabrina; Lazzarin, Adriano; Fortis, Claudio

doi:10.1111/j.1365-3083.2005.01659.x

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…Consistent with previous observations, 25,[28][29][30]44,45 we found that CHI individuals showed reduced NK cell functional activity (reduced CD107a granule exocytosis) against K562 targets in comparison with PHI and HN individuals, and this was restricted to the CD56 dim subset. This may be partially explained by the reduction in the percentage of CD56 dim NK cells with NCRs that occurs with the progression of HIV infection, as well as by the reduced surface expression of NKG2D and NKp46 receptors.…”

Section: Discussionsupporting

confidence: 92%

Perturbation of the natural killer cell compartment during primary human immunodeficiency virus 1 infection primarily involving the CD56^bright subset

Mantegani¹,

Tambussi

Galli

et al. 2010

Immunology

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SummaryWe investigated the distribution of natural killer (NK) cell subsets, their activating and inhibitory receptors, and their cytolytic potential, in primary human immunodeficiency virus (HIV)-infected (PHI) individuals at baseline and during 1 year of follow-up with or without antiretroviral therapy, and compared the results with those obtained in treatment-naïve, chronically HIV-infected (CHI) individuals, and HIV-seronegative (HN) healthy individuals. The proportion of the CD56 dim and CD56 bright subsets decreased with disease progression, whereas that of the CD56 ) CD16 + subset increased. In the CD56 dim subset, the proportion of cells with natural cytotoxicity receptors (NCRs) decreased with disease progression, and their cytolytic potential was reduced. Conversely, the CD56 bright subset was characterized by a high proportion of NCR-positive, killer cell immunoglobulin-like receptor (KIR)-positive NKG2A + cells in both CHI and PHI individuals, which was associated with an increase in their cytolytic potential. During the 1 year of follow-up, the PHI individuals with high viraemia levels and low CD4 + T-cell counts who received highly active antiretroviral therapy (HAART) had a similar proportion of NK subsets to CHI individuals, while patients with low viraemia levels and high CD4 + T-cell counts who remained untreated had values similar to those of the HN individuals. Our results indicate a marked perturbation of the NK cell compartment during HIV-1 infection that is multifaceted, starts early and is progressive, primarily involves the CD56 bright subset, and is partially corrected by effective HAART.

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Section: Discussionsupporting

confidence: 92%

Perturbation of the natural killer cell compartment during primary human immunodeficiency virus 1 infection primarily involving the CD56^bright subset

Mantegani¹,

Tambussi

Galli

et al. 2010

Immunology

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“…An increased number of CD16 + NK cells has been reported in patients with fulminant hepatitis (34). In addition, NK cells may also participate in the development of HBV-related acute liver failure in HIV-positive patients with severe immunodeficiency (35). In our study, patients with HBV-ACLF had more CD3 2 CD57 + NK cells and enhanced expression of FasL in liver and significantly increased expression of NK cell NCRs (NKp30 and NKp46) peripherally, compared with patients with mild CHB.…”

Section: Cd16mentioning

confidence: 99%

Increased Killing of Liver NK Cells by Fas/Fas Ligand and NKG2D/NKG2D Ligand Contributes to Hepatocyte Necrosis in Virus-Induced Liver Failure

Zou¹,

Chen²,

Han³

et al. 2009

The Journal of Immunology

118

113

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The role of liver NK cells in virus-induced severe viral hepatitis and, subsequently, hepatic failure is not well defined. In this study, we investigated the role of liver NK cells in the development of hepatocyte necrosis in fulminant hepatic failure (FHF)and acute-on-chronic liver failure (ACLF) because of viral infection. A mouse model of FHF induced by murine hepatitis virus strain 3 (MHV-3) was used to study the role of liver NK cells. Samples from patients with hepatitis B virus-related ACLF (HBV-ACLF) were examined. After MHV-3 infection, the number of NK cells in livers of BALB/cJ mice increased markedly, peaked at 48 h postinfection, and remained at a high level until sacrifice. In peripheral blood, spleen, and bone marrow, this number decreased significantly. Expression of CD69, cytotoxic activity, and intracellular IFN-γ and TNF-α production by liver NK cells at 48 h postinfection were all significantly upregulated. Depletion of NK cells 24 h post-MHV-3 infection increased the mice survival from 0 of 18 (0%) to 4 of 18 (22.2%). Highly activated liver NK cells were cytotoxic to MHV-3-infected hepatocytes and this effect was markedly inhibited by anti-Fas ligand (FasL) plus anti-NKG2D mAbs. Furthermore, the accumulation of hepatic NK cells and increased expression of FasL and natural cytotoxicity receptors (NKp30 and NKp46) on the peripheral NK cells from patients with HBV-ACLF were correlated with disease progression. These results indicate NK cells play a pivotal role in the pathogenesis of FHF and HBV-ACLF, in which process Fas/FasL and NKG2D/NKG2D ligand pathway contribute to the liver NK cell-mediated hepatocyte injury.

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“…Activation of the NK-cell-mediated cytotoxicity pathway during HBV infection could result in liver damage and contribute to the development of HBV-ALF. 24 However, the potential mechanism has remained obscure. Others have shown that during the processes of HBV-ALF or FHF, the KCTD9, Fas/FasL, NKG2D/NKG2D ligand and TRAIL pathways 25 - 27 interact with the NK cell-mediated cytotoxicity pathway and contribute to hepatocyte injury.…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes and Potential Molecular Mechanisms in Patients with HBV-Associated Acute Liver Failure

Sun

et al. 2020

Evol Bioinform Online

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Hepatitis B virus (HBV) infection is a major cause of acute liver failure (ALF) in China, and mortality rates are high among patients who do not receive a matched liver transplant. This study aimed to determine potential mechanisms involved in HBV-ALF pathogenesis. Gene expression profiles under access numbers GSE38941 and GSE14668 were downloaded from the Gene Expression Omnibus database, including cohorts of HBV-ALF liver tissue and normal samples. Differentially expressed genes (DEGs) with false discovery rates (FDR) <0.05 and |log2(fold change)| >1 as thresholds were screened using the Limma package. Gene modules associated with stable disease were mined using weighed gene co-expression network analysis (WGCNA). A co-expression network was constructed and DEGs were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A gene-based network was constructed to explore major factors associated with disease progression. We identified 2238 overlapping DEGs as crucial gene cohorts in ALF development. Based on a WGCNA algorithm, 10 modules (modules 1-10) were obtained that ranged from 75 to 1078 genes per module. Cyclin-dependent kinase 1 ( CDK1), cyclin B1 ( CCNB1), and cell-division cycle protein 20 ( CDC20) hub genes were screened using the co-expression network. Furthermore, 17 GO terms and 6 KEGG pathways were identified, such as cell division, immune response process, and antigen processing and presentation. Two overlapping signaling pathways that are crucial factors in HBV-ALF were screened using the Comprehensive Toxicogenomics Database (CTD). Several candidate genes including HLA-E, B2M, HLA-DPA1, and SYK were associated with HBV-ALF progression. Natural killer cell-mediated cytotoxicity and antigen presentation contributed to the progression of HBV-ALF. The HLA-E, B2M, HLA-DPA1, and SYK genes play critical roles in the pathogenesis and development of HBV-ALF.

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Natural Killer‐Cell Cytotoxicity in HIV‐Positive and HIV‐Negative Patients with and Without Severe Course of Hepatitis B Virus Infection

Cited by 6 publications

References 41 publications

Perturbation of the natural killer cell compartment during primary human immunodeficiency virus 1 infection primarily involving the CD56^bright subset

Perturbation of the natural killer cell compartment during primary human immunodeficiency virus 1 infection primarily involving the CD56^bright subset

Increased Killing of Liver NK Cells by Fas/Fas Ligand and NKG2D/NKG2D Ligand Contributes to Hepatocyte Necrosis in Virus-Induced Liver Failure

Identification of Hub Genes and Potential Molecular Mechanisms in Patients with HBV-Associated Acute Liver Failure

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Natural Killer‐Cell Cytotoxicity in HIV‐Positive and HIV‐Negative Patients with and Without Severe Course of Hepatitis B Virus Infection

Cited by 6 publications

References 41 publications

Perturbation of the natural killer cell compartment during primary human immunodeficiency virus 1 infection primarily involving the CD56bright subset

Perturbation of the natural killer cell compartment during primary human immunodeficiency virus 1 infection primarily involving the CD56bright subset

Increased Killing of Liver NK Cells by Fas/Fas Ligand and NKG2D/NKG2D Ligand Contributes to Hepatocyte Necrosis in Virus-Induced Liver Failure

Identification of Hub Genes and Potential Molecular Mechanisms in Patients with HBV-Associated Acute Liver Failure

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Perturbation of the natural killer cell compartment during primary human immunodeficiency virus 1 infection primarily involving the CD56^bright subset

Perturbation of the natural killer cell compartment during primary human immunodeficiency virus 1 infection primarily involving the CD56^bright subset