Influence of <i><scp>KIR</scp></i> genes and their <scp>HLA</scp> ligands in susceptibility to dengue in a population from southern Brazil

Beltrame, Letícia Maria; Sell, Ana Maria; Moliterno, Ricardo Alberto; Clementino, Samaia Laface; Cardozo, Daniela Máira; Dalálio, M. M. O.; Fonzar, Udelysses Janete Veltrini; Visentainer, Jeane Eliete Laguila

doi:10.1111/tan.12256

Cited by 29 publications

(27 citation statements)

References 35 publications

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“…Thus, increased NK cell activity might reduce viral replication in the earlier stages of infection, leading to clinically inapparent and/or milder forms of disease requiring no hospitalization. In contrast to our results, a recent study has shown the association of KIR2DL5, KIR2DS1 and KIR2DS5 genes with DF in a Brazilian population (Beltrame et al, 2013). This could be due to the difference in the circulating viral serotypes/genotypes, immune status of the patients and the clinical categories of patients compared.…”

Section: Discussioncontrasting

confidence: 99%

Profile of killer cell immunoglobulin‐like receptor and its human leucocyte antigen ligands in dengue‐infected patients from Western India

Alagarasu

Bachal

Shah

et al. 2015

Int J Immunogenetics

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Killer cell immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells (NKs). Qualitative and quantitative differences in the type and the number of KIRs expressed on NK cells affect its activation which would influence the outcome of the disease. In this study, 114 hospitalized cases of dengue [82 dengue fever (DF) and 32 dengue haemorrhagic fever (DHF) cases] and 104 healthy controls (HC) without no known history of hospitalization for dengue-like illness were investigated for their KIR gene profile to find out the association of KIR genes with dengue disease severity. KIR gene profile was investigated using duplex sequence-specific priming polymerase chain reaction-based typing system. The results revealed a higher frequency of KIR3DL1 gene [P = 0.0225; odds ratio (OR) 4.1 95% confidence interval (CI) 1.1-14.8] and lower frequency of KIR3DS1/3DS1 genotype [P = 0.0225; OR 0.24 95% CI (0.068-0.88)] in DF cases compared to HC. Immunoglobulin-like receptor gene frequencies were not different between DHF and DF or HC. The results suggest that KIR3DL1/KIR3DS1 locus might be associated with the risk of developing DF.

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Section: Discussioncontrasting

confidence: 99%

Profile of killer cell immunoglobulin‐like receptor and its human leucocyte antigen ligands in dengue‐infected patients from Western India

Alagarasu

Bachal

Shah

et al. 2015

Int J Immunogenetics

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“…The KIR:HLA‐C axis appears to be important in controlling the outcome of HCV infection. Furthermore, the KIR2DL3:group 1 HLA‐C has also been shown to be protective against dengue virus infection in Brazil, suggesting it may be important for other positive strand RNA . As discussed above, this protection could be related to the lower affinity of KIR2DL3 for HLA‐C and the increased sensitivity of KIR2DL3‐positive NK cells to changes in the peptide content of MHC class I .…”

Section: Nk Cell Receptors In Diseasementioning

confidence: 95%

“…The mechanism of antagonism is not clear, but several models exist . Tight clustering of KIRs at the cell surface is required for inhibitory signaling.…”

Section: Kirmentioning

confidence: 99%

NK cells: tuned by peptide?

Das

Khakoo

2015

Immunological Reviews

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Natural killer cells express multiple receptors for major histocompatibility complex (MHC) class I, including the killer cell immunoglobulin-like receptors (KIRs) and the C-type lectin-like CD94:NKG2 receptors. The KIR locus is extremely polymorphic, paralleling the diversity of its classical MHC class I ligands. Similarly, the conservation of the NKG2 family of receptors parallels the conservation of MHC-E, the ligand for CD94:NKG2A/C/E. Binding of both CD94:NKG2 heterodimers and KIR to their respective MHC class I ligand is peptide dependent, and despite the evolution of these receptors, they have retained the property of peptide selectivity. Such peptide selectivity affects these two systems in different ways. HLA-E binding non-inhibitory peptides augment inhibition at CD94:NKG2A, while HLA-C binding non-inhibitory peptides antagonize inhibition at KIR2DL2/3, implying that KIRs are specialized to respond positively to changes in peptide repertoire. Thus, while specific KIRs, such as KIR2DL3, are associated with beneficial outcomes from viral infections, viral peptides augment inhibition at CD94:NKGA. Conversely, NKG2A-positive NK cells sense MHC class I downregulation more efficiently than KIRs. Thus, these two receptor:ligand systems appear to have complementary functions in recognizing changes in MHC class I.

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“…These latter proteins are up-regulated in stressed cells and interact with NKG2D, an activating receptor on NK cells. More recently, two small genetic studies evaluated associations between KIR-ligand pairs and susceptibility to dengue in Gabon and Southern Brazil [23,24]. Petitdemange et al found no evidence of a role for KIR genotypes in patients infected with DENV-2.…”

Section: Introductionmentioning

confidence: 99%

Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells

Townsley

O’Connor

Cosgrove

et al. 2015

Clinical and Experimental Immunology

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SummaryKiller immunoglobulin‐like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells. The functional importance of KIR–HLA interactions has been demonstrated for a number of chronic viral infections, but to date only a few studies have been performed in the context of acute self‐limited viral infections. During our investigation of CD8+ T cell responses to a conserved HLA‐B57‐restricted epitope derived from dengue virus (DENV) non‐structural protein‐1 (NS1), we observed substantial binding of the tetrameric complex to non‐T/non‐B lymphocytes in peripheral blood mononuclear cells (PBMC) from a long‐standing clinical cohort in Thailand. We confirmed binding of the NS1 tetramer to CD56dim NK cells, which are known to express KIRs. Using depletion studies and KIR‐transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory receptor KIR3DL1. Phenotypical analysis of PBMC from HLA‐B57+ subjects with acute DENV infection revealed marked activation of NS1 tetramer‐binding natural killer (NK) cells around the time of defervescence in subjects with severe dengue disease. Collectively, our findings indicate that subsets of NK cells are activated relatively late in the course of acute DENV illness and reveal a possible role for specific KIR–HLA interactions in the modulation of disease outcomes.

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Influence of KIR genes and their HLA ligands in susceptibility to dengue in a population from southern Brazil

Cited by 29 publications

References 35 publications

Profile of killer cell immunoglobulin‐like receptor and its human leucocyte antigen ligands in dengue‐infected patients from Western India

Profile of killer cell immunoglobulin‐like receptor and its human leucocyte antigen ligands in dengue‐infected patients from Western India

NK cells: tuned by peptide?

Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells

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