NK cells express both inhibitory and activatory receptors that allow them to recognize target cells through HLA class I Ag expression. KIR3DL1 is a receptor that recognizes the HLA-Bw4 public epitope of HLA-B alleles. We demonstrate that polymorphism within the KIR3DL1 receptor has functional consequences in terms of NK cell recognition of target. Inhibitory alleles of KIR3DL1 differ in their ability to recognize HLA-Bw4 ligand, and a consistent hierarchy of ligand reactivity can be defined. KIR3DS1, which segregates as an allele of KIR3DL1, has a short cytoplasmic tail characteristic of activatory receptors. Because it is very similar to KIR3DL1 in the extracellular domains, it has been assumed that KIR3DS1 will recognize a HLA-Bw4 ligand. In this study, we demonstrate that KIR3DS1 is expressed as a protein at the cell surface of NK cells, where it is recognized by the Z27 Ab. Using this Ab, we found that KIR3DS1 is expressed on a higher percentage of NK cells in KIR3DS1 homozygous compared with heterozygous donors. In contrast to the inhibitory KIR3DL1 allotypes, KIR3DS1 did not recognize HLA-Bw4 on EBV-transformed cell lines.

Hepatitis C is a common infection with significant morbidity and mortality, and only a minority of patients successfully clear the infection. Identification of factors that influence disease progression in HCV infection is difficult owing to the lack of well-defined patient cohorts. However, recent evidence supports a role for the innate immune system in virus clearance. In this study, we investigated innate immune genes for their contribution to disease progression in a unique cohort of well-controlled HCV-infected patients. The Irish cohort of HCV patients is uniquely homogenous; patients were infected with a single genotype of HCV from contaminated anti-D Ig. We genotyped 543 infected patients, including 247 patients who spontaneously resolved infection, for natural killer (NK) cellassociated killer cell Ig-like receptors (KIR) genes and the recently reported IL28B (IFNλ3) SNP. The NK cell gene KIR2DS3 was significantly increased in patients with chronic infection [odds ratio (OR) 1.90, 95% confidence interval (CI) 1.25-2.90, P < 0.002]. The IL28B "T" allele was also significantly increased in chronically infected patients (OR 7.38, 95% CI 4.93-11.07, P < 10). The presence of both markers synergized to significantly increase the risk of chronic infection over either factor alone (OR 20.11, 95% CI 9.05-44.68, P < 10 −7). In functional experiments, we found that IL28A significantly inhibited IFN-γ production by NK cells. Thus, we demonstrate a functional link between NK cells and type 3 IFN. Our findings may contribute to the development of a prognostic test for HCV and identify therapeutic strategies for the clinical management of HCV-infected patients.

Natural killer (NK) cells are lymphocytes that function as part of the innate immune system. Their activity is controlled by a range of inhibitory and activating receptors, including the important killer-cell immunoglobulin-like receptors (KIR). The KIR are a multi-gene family of receptors that interact with the human leukocyte antigen (HLA) class I family of molecules and are characterised by extensive allelic polymorphism. Their expression on the cell surface of NK cells is highly variable, but the factors responsible for this variability are not yet clearly understood. In the current study, we investigated KIR expression in a healthy human cohort that we had previously characterised in depth at a genetic level, with KIR allele typing and HLA class I ligand genotypes available for all donors (n=198). Allelic polymorphism significantly affected the phenotypic expression of all KIR analysed, whereas HLA ligand background influenced the expression levels of 2DL1 and 2DL3. In particular, we found that although 2DL2 may influence 2DL1 expression, this appears to be owing to variation in 2DL1 copy number. Finally, the inhibitory receptor LILRB1 had higher expression levels in individuals with B/B KIR genotypes, suggesting a possible relationship between KIR and non-KIR receptors, which serves to balance NK cell activation potential.

Abiotic stresses cause oxidative damage in plants. Here, we demonstrate that foliar application of an extract from the seaweed Ascophyllum nodosum, SuperFifty (SF), largely prevents paraquat (PQ)-induced oxidative stress in Arabidopsis thaliana. While PQ-stressed plants develop necrotic lesions, plants pre-treated with SF (i.e., primed plants) were unaffected by PQ. Transcriptome analysis revealed induction of reactive oxygen species (ROS) marker genes, genes involved in ROS-induced programmed cell death, and autophagy-related genes after PQ treatment. These changes did not occur in PQ-stressed plants primed with SF. In contrast, upregulation of several carbohydrate metabolism genes, growth, and hormone signaling as well as antioxidant-related genes were specific to SF-primed plants. Metabolomic analyses revealed accumulation of the stress-protective metabolite maltose and the tricarboxylic acid cycle intermediates fumarate and malate in SF-primed plants. Lipidome analysis indicated that those lipids associated with oxidative stress-induced cell death and chloroplast degradation, such as triacylglycerols (TAGs), declined upon SF priming. Our study demonstrated that SF confers tolerance to PQ-induced oxidative stress in A. thaliana, an effect achieved by modulating a range of processes at the transcriptomic, metabolic, and lipid levels.

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As the world develops and population increases, so too does the demand for higher agricultural output with lower resources. Plant biostimulants appear to be one of the more prominent sustainable solutions, given their natural origin and their potential to substitute conventional methods in agriculture. Classified based on their source rather than constitution, biostimulants such as humic substances (HS), protein hydrolysates (PHs), seaweed extracts (SWE) and microorganisms have a proven potential in improving plant growth, increasing crop production and quality, as well as ameliorating stress effects. However, the multi-molecular nature and varying composition of commercially available biostimulants presents challenges when attempting to elucidate their underlying mechanisms. While most research has focused on the broad effects of biostimulants in crops, recent studies at the molecular level have started to unravel the pathways triggered by certain products at the cellular and gene level. Understanding the molecular influences involved could lead to further refinement of these treatments. This review comprises the most recent findings regarding the use of biostimulants in plants, with particular focus on reports of their molecular influence.

No abstract

Natural killer (NK) cells are lymphocytes of the innate immune system. In humans, NK cell activities are partly controlled by the diverse killer immunoglobulin-like receptor (KIR) gene family. The importance of NK cells in both immunity to infection and reproduction makes KIR strong candidates for genes undergoing dynamic evolution in the human genome. Using highresolution allelic typing, we investigated the potential role of natural selection in the diversification of KIR in the Irish population. Higher diversity than expected is observed at several loci, consistent with a history of balancing selection acting to maintain several allelic variants at high frequency in the population. KIR diversity is enhanced further at the haplotype level with functional polymorphisms at KIR2DL4, KIR3DL1 and KIR2DS4 defining nine 'core' haplotypes. Analysis of these core haplotypes in combination with human leukocyte antigen (HLA) class I ligands revealed several nonrandom associations. In particular, the KIR:HLA association for the core haplotype defined by KIR3DL1*01502 was female specific and a likely consequence of negative selection acting against KIR3DL1*01502 on an HLA-C1/C1 background. Many of the associations between KIR and HLA in the Irish differ from those previously reported, which argues against universal selective pressures for specific KIR:HLA combinations in diverse human populations.