IL-4, IL-13 and IFN-γ -induced genes in highly purified human neutrophils

Interleukin (IL)-4 and IL-13 are related cytokines with well-known specific roles in type 2 immune response. However, their effects on neutrophils are not completely understood. For this, we studied human primary neutrophil responses to IL-4 and IL-13. Neutrophils are dose-dependently responsive to both IL-4 and IL-13 as indicated by signal transducer and activator of transcription 6 (STAT6) phosphorylation upon stimulation, with IL-4 being more potent inducer of STAT6. IL-4-, IL-13- and Interferon (IFN)-γ-stimulated gene expression in highly purified human neutrophils induced both overlapping and unique gene expression in highly purified human neutrophils. IL-4 and IL-13 specifically regulate several immune-related genes, including IL-10, tumor necrosis factor (TNF) and leukemia inhibitory factor (LIF), while type1 immune response-related IFN-γ induced gene expression related for example, to intracellular infections. In analysis of neutrophil metabolic responses, oxygen independent glycolysis was specifically regulated by IL-4, but not by IL-13 or IFN-γ, suggesting specific role for type I IL-4 receptor in this process. Our results provide a comprehensive analysis of IL-4, IL-13 and IFN-γ -induced gene expression in neutrophils while also addressing cytokine-mediated metabolic changes in neutrophils.publishedVersionPeer reviewe

IFNL3 (IL28B) favorable genotype escapes hepatitis C virus-induced microRNAs and mRNA decay

The IFNL3 (IL28B) gene has received immense attention in the hepatitis C virus (HCV) field as multiple independent genome-wide association studies identified a strong association between polymorphisms near the IFNL3 gene and HCV clearance. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) located in the 3′ untranslated region (3′ UTR) of the IFNL3 mRNA that dictates transcript stability. This polymorphism influences AU-rich element-mediated decay as well as the binding of HCV-induced microRNAs during infection. Together, these pathways mediate robust repression of the unfavorable IFNL3 genotype. These data reveal a novel mechanism by which HCV attenuates the antiviral response and uncover new potential therapeutic targets for HCV treatment

Endomembrane targeting of human OAS1 p46 augments antiviral activity

Many host RNA sensors are positioned in the cytosol to detect viral RNA during infection. However, most positive-strand RNA viruses replicate within a modified organelle co-opted from intracellular membranes of the endomembrane system, which shields viral products from cellular innate immune sensors. Targeting innate RNA sensors to the endomembrane system may enhance their ability to sense RNA generated by viruses that use these compartments for replication. Here, we reveal that an isoform of oligoadenylate synthetase 1, OAS1 p46, is prenylated and targeted to the endomembrane system. Membrane localization of OAS1 p46 confers enhanced access to viral replication sites and results in increased antiviral activity against a subset of RNA viruses including flaviviruses, picornaviruses, and SARS-CoV-2. Finally, our human genetic analysis shows that the OAS1 splice-site SNP responsible for production of the OAS1 p46 isoform correlates with protection from severe COVID-19. This study highlights the importance of endomembrane targeting for the antiviral specificity of OAS1 and suggests that early control of SARS-CoV-2 replication through OAS1 p46 is an important determinant of COVID-19 severity

Interferon Lambda Genetics and Biology in Regulation of Viral Control

Type III interferons, also known as interferon lambdas (IFNλs), are the most recent addition to the IFN family following their discovery in 2003. Initially, IFNλ was demonstrated to induce expression of interferon-stimulated genes and exert antiviral properties in a similar manner to type I IFNs. However, while IFNλ has been described to have largely overlapping expression and function with type I IFNs, it has become increasingly clear that type III IFNs also have distinct functions from type I IFNs. In contrast to type I IFNs, whose receptor is ubiquitously expressed, type III IFNs signal and function largely at barrier epithelial surfaces, such as the respiratory and gastrointestinal tracts, as well as the blood–brain barrier. In further support of unique functions for type III IFNs, single nucleotide polymorphisms in IFNL genes in humans are strongly associated with outcomes to viral infection. These biological linkages have also been more directly supported by studies in mice highlighting roles of IFNλ in promoting antiviral immune responses. In this review, we discuss the current understanding of type III IFNs, and how their functions are similar to, and different from, type I IFN in various immune cell subtypes and viral infections

Antimicrobial, antioxidant and anticancer activities of gold nanoparticles green synthesized using Mangifera indica seed aqueous extract

AbstractIn this study, gold nanoparticles (AuNPs) were synthesised using seed extract of mango (Mangifera indica) which is considered as waste and generally thrown away into the environment. The bioactive molecules in the seed act as reducing agent to synthesise AuNPs without using any external agent. The characterisation of green synthesised AuNPs was done using various spectroscopic techniques. Visual colour change from colourless to ruby red colour confirmed the formation of AuNPs which was further confirmed by maximum absorption peak at 550 nm by UV-spectra. Crystalline nature was confirmed by XRD technique while round, triangle and irregular shape and 19.45 nm size was confirmed by TEM and SAED analysis. FTIR analysis confirmed the presence of alcohol or phenol, carboxylic acid, ketones, amines, aromatic amines, aliphatic amines, alkyl halides and alkynes in M. indica seed which were responsible for the reduction of gold to AuNPs. The green synthesised AuNPs were evaluated for their antimicrobial, antioxidant and cytotoxic potential. They showed moderate antibacterial, cytotoxic and dose-dependent antioxidant activity. Seeds of M. indica instead of discarding can be successfully utilised for AuNPs synthesis which can be used as a natural source of antimicrobial, antioxidant and anticancer agent.HighlightsGreen synthesis of gold nanoparticles (AuNPs) from fruit (Mangifera indica) waste (seed).Characterisation using various spectroscopic techniques: UV-Vis spectroscopy, Zeta potential, FTIR, XRD and TEM analysis.Synthesized AuNPs were round, triangle and irregular in shape and 19.45 nm in size.Antimicrobial activity of AuNPs against 14 microorganisms.Antioxidant activity of AuNPs in terms of DPPH, SO and ABTS.Cytotoxic activity against HeLa, MCF-7 and fibroblast normal cell lines