Increased expressions of NKp44, NKp46 on NK/NKT-like cells are associated with impaired cytolytic function in self-limiting hepatitis E infection

Das, Rumki; Tripathy, Anuradha S.

doi:10.1007/s00430-014-0338-1

Cited by 24 publications

(19 citation statements)

References 42 publications

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“…These results are consistent with another study that shows NKp30 and NKp46 are expressed on non-activated and activated NK cells, whereas NKp44 is expressed preferentially after in vitro activation [42, 43]. Moreover, following Hepatitis E virus infection an increased expression of NKp44, NKp46 on NK/NKT-like cells were associated with decreased cytolytic activity [44]. It should be also mentioned that in addition to the cytolytic function of NCR1, this receptor is also important for the cross talk with antigen presenting cells in general and DCs in particular, and affect the cytokine milieu that is created during the development of inflammation, as previously described [45].…”

Section: Discussionsupporting

confidence: 91%

Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation

et al. 2016

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The function of NCR1 was studied in a model of experimental asthma, classified as a type 1 hypersensitivity reaction, in mice. IgE levels were significantly increased in the serum of OVA immunized NCR1 deficient (NCR1gfp/gfp) mice in comparison to OVA immunized wild type (NCR1+/+) and adjuvant immunized mice. Histological analysis of OVA immunized NCR1gfp/gfp mice revealed no preservation of the lung structure and overwhelming peribronchial and perivascular granulocytes together with mononuclear cells infiltration. OVA immunized NCR+/+ mice demonstrated preserved lung structure and peribronchial and perivascular immune cell infiltration to a lower extent than that in NCR1gfp/gfp mice. Adjuvant immunized mice demonstrated lung structure preservation and no immune cell infiltration. OVA immunization caused an increase in PAS production independently of NCR1 presence. Bronchoalveolar lavage (BAL) revealed NCR1 dependent decreased percentages of eosinophils and increased percentages of lymphocytes and macrophages following OVA immunization. In the OVA immunized NCR1gfp/gfp mice the protein levels of eosinophils’ (CCL24) and Th2 CD4+ T-cells’ chemoattractants (CCL17, and CCL24) in the BAL are increased in comparison with OVA immunized NCR+/+ mice. In the presence of NCR1, OVA immunization caused an increase in NK cells numbers and decreased NCR1 ligand expression on CD11c+GR1+ cells and decreased NCR1 mRNA expression in the BAL. OVA immunization resulted in significantly increased IL-13, IL-4 and CCL17 mRNA expression in NCR1+/+ and NCR1gfp/gfp mice. IL-17 and TNFα expression increased only in OVA-immunized NCR1+/+mice. IL-6 mRNA increased only in OVA immunized NCR1gfp/gfp mice. Collectively, it is demonstrated that NCR1 dampens allergic eosinophilic airway inflammation.

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Section: Discussionsupporting

confidence: 91%

Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation

et al. 2016

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“…NKT-like cells are a subset of αβ T cells that express NK activation receptors and also exhibit a highly specialized effector memory phenotype (Peralbo et al, 2007 ; Tang et al, 2013 ). The functional activity of NK/NKT-like cells is regulated through their repertoire of activation (NKG2C, NKG2D, NKp30, NKp44, and NKp46) and inhibitory (CD158a, CD158b, KIR3DL1, and NKG2A) receptors, which recognize ligands on the surface of target cells (Peralbo et al, 2007 ; Watzl and Long, 2010 ; Das and Tripathy, 2014 ). Upon activation, both NK and NKT-like cells produce inflammatory cytokines, such as IFN-γ, and lyse target cells by exocytosis of perforin and granzyme, leading to inhibition of viral replication and enhancement of cytotoxicity against target cells (Biron and Brossay, 2001 ; Janeway and Medzhitov, 2002 ; Peralbo et al, 2007 ; Das and Tripathy, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Phenotypic and functional analyses of NK and NKT-like populations during the early stages of chikungunya infection

2015

Self Cite

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The aim of this study was to characterize NK (CD56+CD3−) and NKT-like cell (CD56+CD3+) responses early after chikungunya infection. Expression profiling and functional analysis of T/NK/NKT-like cells were performed on samples from 56 acute and 31 convalescent chikungunya patients and 56 control individuals. The percentages of NK cells were high in both patient groups, whereas NKT-like cell percentages were high only in the convalescent group. The percentages of NKp30+CD3−CD56+, NKp30+CD3+CD56+, CD244+CD3−CD56+, and CD244+CD3+CD56+cells were high, whereas the percentages of NKG2D+CD3−CD56+ and NKG2D+CD3+CD56+cells were low in both patient groups. The percentages of NKp44+CD3−CD56+ cells were high in both patient groups, whereas the percentages of NKp44+CD3+CD56+ cells were higher in the acute group than in convalescent and control groups. The percentages of NKp46+CD3−CD56+ cells were high in both patient groups. Higher percentages of perforin+CD3−CD56+ and perforin+CD3+CD56+ cells were observed in acute and convalescent patients, respectively. Higher cytotoxic activity was observed in acute patients than in controls. IFN-γ expression on NK cells of convalescent patients and on NKT-like cells of both patient groups was indicative of the regulatory role of NK and NKT-like cells. Collectively, these data showed that higher expression of activating receptors on NK/NKT-like cells and perforin+ NK cells in acute patients could be responsible for increased cytotoxicity. The observed expression of perforin+ NK cells in the acute phase and IFN-γ+ NKT-like cells in the subsequent convalescent stage showed that NK/NKT-like cells mount an early and efficient response to chikungunya virus. Further study of the molecular mechanisms that limit viral dissemination/establishment of chronic disease will aid in understanding how NK/NKT-like cells control chikungunya infection.

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“…CD1d alone was detected in self-recovering PR patients during the acute phase and was part of pregnancy-associated immunomodulation. Previously our lab recorded higher proportion of activated CD16+ Cd56+/CD3+ cells in the NPR patients [62]. In view of this, it is interesting to note that in a transgenic HBV transfer mouse model, induction of acute hepatitis was mediated by CD1D-restricted NKT cells [63].…”

Section: Discussionmentioning

confidence: 85%

The expression patterns of immune response genes in the Peripheral Blood Mononuclear cells of pregnant women presenting with subclinical or clinical HEV infection are different and trimester-dependent: A whole transcriptome analysis

Ramdasi¹,

Arankalle²

2020

PLoS ONE

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Hepatitis E is an enteric disease highly prevalent in the developing countries. The basis for high mortality among pregnant hepatitis E patients remains unclear. Importantly, a large proportion of infected pregnant women present with subclinical infection as well. In order to understand the possible mechanisms influencing clinical presentation of hepatitis E in pregnant women, we explored a system biology approach. For this, PBMCs from various categories were subjected to RNAseq analysis. These included non-pregnant (NPR, acute and convalescent phases) and pregnant (PR, 2 nd and 3 rd trimesters, acute phase and subclinical HEV infections) patients and corresponding healthy controls. The current study deals with immune response genes.In contrast to exclusive up-regulation of nonspecific, early immune response transcripts in the NPR patients, the PR patients exhibited broader and heightened expression of genes associated with innate as well as adaptive T and B cell responses. The study identified for the first time (1) inverse relationship of immunoglobulin (Ig) genes overexpression and (2) association of differential expression of S100 series genes with disease presentation. The data suggests possible involvement of TLR4 and NOD1 in pregnant patients and alpha defensins in all patient categories suggesting a role in protection. Induction of IFNγ gene was not detected during the acute phase irrespective of pregnancy. Association of response to vitamin D, transcripts related to NK/NKT and regulatory T cells during subclinical infection are noteworthy.The data obtained here could be correlated with several studies reported earlier in hepatitis E patients suggesting utility of PBMCs as an alternate specimen. The extensive, informative data provided here for the first time should form basis for future studies that will help in understanding pathogenesis of fulminant hepatitis E.

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Increased expressions of NKp44, NKp46 on NK/NKT-like cells are associated with impaired cytolytic function in self-limiting hepatitis E infection

Cited by 24 publications

References 42 publications

Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation

Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation

Phenotypic and functional analyses of NK and NKT-like populations during the early stages of chikungunya infection

The expression patterns of immune response genes in the Peripheral Blood Mononuclear cells of pregnant women presenting with subclinical or clinical HEV infection are different and trimester-dependent: A whole transcriptome analysis

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