The CD56−CD16+ NK cell subset in chronic infections

Guethlein, Lisbeth A.; Parham, Peter

doi:10.1042/bst20221374

Cited by 4 publications

(2 citation statements)

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“…We identified the main NK cells subsets by the expression of CD16 and CD56. CD16 is a low-affinity receptor for immunoglobulin G type III (FcγRIII) that mediates the cellular antibody-dependent cytotoxicity mechanism [ 26 , 27 ]. Glycoprotein CD56 (NCAM, NKH-1, Leu-19) belongs to the immunoglobulin superfamily and participates in intercellular contacts [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Association of Blood NK Cell Phenotype with the Severity of Liver Fibrosis in Patients with Chronic Viral Hepatitis C with Genotype 1 or 3

Tsukanov,

Savchenko,

Cherepnin

et al. 2024

Diagnostics

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Background: NK cells phenotype and functional state in different genotypes of chronic viral hepatitis C (CVHC), depending on liver fibrosis severity, have not been sufficiently studied, which limits the possibilities for the development of pathology therapy. Methods: The CVHC diagnosis was based on the EASL recommendations (2018). Clinical examination with liver elastometry was performed in 297 patients with genotype 1 and in 231 patients with genotype 3 CVHC. The blood NK cells phenotype was determined by flow cytometry in 74 individuals with genotype 1 and in 69 individuals with genotype 3 CVHC. Results: The frequency of METAVIR liver fibrosis stages F3–F4 was 32.5% in individuals with genotype 3, and 20.5% in individuals with genotype 1 CVHC (p = 0.003). In patients with both genotype 1 and genotype 3 CVHC, a decrease in the total number of blood NK cells, CD56brightCD16+ NK cells and an increase in the proportion of CD56dimCD16+ NK cells, CD94+ and CD38 + CD73+ NK cells were registered in patients with fibrosis stage F3–F4 by METAVIR in comparison with persons with METAVIR fibrosis stage F0–F1. Conclusions: In patients with both genotype 1 and genotype 3 CVHC, an imbalance in the ratio between cytokine-producing and cytotoxic NK cells and an increase in the content of NK cells that express inhibitory molecules were determined in patients with severe liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Association of Blood NK Cell Phenotype with the Severity of Liver Fibrosis in Patients with Chronic Viral Hepatitis C with Genotype 1 or 3

Tsukanov,

Savchenko,

Cherepnin

et al. 2024

Diagnostics

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“…The CD56 neg NK cell population is also known to expand in other chronic viral infections including hepatitis C virus (HCV), Epstein-Barr virus (EBV), and chronic cytomegalovirus (CMV). This observation suggests that it is likely a common feature among chronic viral infections ( 80 ).…”

Section: Nk Cells During Viral Infectionmentioning

confidence: 96%

NK cell subsets and dysfunction during viral infection: a new avenue for therapeutics?

Bjorgen,

Dick,

Cromarty

et al. 2023

Front. Immunol.

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In the setting of viral challenge, natural killer (NK) cells play an important role as an early immune responder against infection. During this response, significant changes in the NK cell population occur, particularly in terms of their frequency, location, and subtype prevalence. In this review, changes in the NK cell repertoire associated with several pathogenic viral infections are summarized, with a particular focus placed on changes that contribute to NK cell dysregulation in these settings. This dysregulation, in turn, can contribute to host pathology either by causing NK cells to be hyperresponsive or hyporesponsive. Hyperresponsive NK cells mediate significant host cell death and contribute to generating a hyperinflammatory environment. Hyporesponsive NK cell populations shift toward exhaustion and often fail to limit viral pathogenesis, possibly enabling viral persistence. Several emerging therapeutic approaches aimed at addressing NK cell dysregulation have arisen in the last three decades in the setting of cancer and may prove to hold promise in treating viral diseases. However, the application of such therapeutics to treat viral infections remains critically underexplored. This review briefly explores several therapeutic approaches, including the administration of TGF-β inhibitors, immune checkpoint inhibitors, adoptive NK cell therapies, CAR NK cells, and NK cell engagers among other therapeutics.

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Natural killer cell antibody‐dependent cellular cytotoxicity to Plasmodium falciparum is impacted by cellular phenotypes, erythrocyte polymorphisms, parasite diversity and intensity of transmission

Tukwasibwe,

Lewis,

Taremwa

et al. 2024

Clin & Trans Imm

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ObjectivesNatural killer (NK) cells make important contributions to anti‐malarial immunity through antibody‐dependent cellular cytotoxicity (ADCC), but the role of different components of this pathway in promoting NK cell activation remains unclear.MethodsWe compared the functions and phenotypes of NK cells from malaria‐exposed and malaria‐naive donors, and then varied the erythrocyte genetic background, Plasmodium falciparum strain and opsonising plasma used in ADCC to observe their impacts on NK cell degranulation as measured by CD107a mobilisation.ResultsNatural killer cells from malaria‐exposed adult Ugandan donors had enhanced ADCC, but an impaired pro‐inflammatory response to cytokine stimulation, compared to NK cells obtained from malaria‐naive adult North American donors. Cellular phenotypes from malaria‐exposed donors reflected this specialisation for ADCC, with a compartment‐wide downregulation of the Fc receptor γ‐chain and enrichment of highly differentiated CD56dim and CD56neg populations. NK cell degranulation was enhanced in response to opsonised P. falciparum schizonts cultured in sickle cell heterozygous erythrocytes relative to wild‐type erythrocytes, and when using opsonising plasma collected from donors living in a high transmission area compared to a lower transmission area despite similar levels of 3D7 schizont‐specific IgG levels. However, degranulation was lowered in response to opsonised field isolate P. falciparum schizonts isolated from clinical malaria infections, compared to the 3D7 laboratory strain typically used in these assays.ConclusionThis work highlights important host and parasite factors that contribute to ADCC efficacy that should be considered in the design of ADCC assays.

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The CD56−CD16+ NK cell subset in chronic infections

Cited by 4 publications

References 154 publications

Association of Blood NK Cell Phenotype with the Severity of Liver Fibrosis in Patients with Chronic Viral Hepatitis C with Genotype 1 or 3

Association of Blood NK Cell Phenotype with the Severity of Liver Fibrosis in Patients with Chronic Viral Hepatitis C with Genotype 1 or 3

NK cell subsets and dysfunction during viral infection: a new avenue for therapeutics?

Natural killer cell antibody‐dependent cellular cytotoxicity to Plasmodium falciparum is impacted by cellular phenotypes, erythrocyte polymorphisms, parasite diversity and intensity of transmission

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