A5039518624- Immune Cell Function and Interaction
- interferon and immune responses
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis C virus research
- Immune Response and Inflammation
- Systemic Lupus Erythematosus Research
- Gut microbiota and health
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Inflammatory Bowel Disease
- Immunotherapy and Immune Responses
- Systemic Sclerosis and Related Diseases
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Long-Term Effects of COVID-19
- Microbial Metabolites in Food Biotechnology
- Helicobacter pylori-related gastroenterology studies
- Receptor Mechanisms and Signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Influenza Virus Research Studies
- Complement system in diseases
- Galectins and Cancer Biology
University of Manitoba
2022-2025
Apotex (Canada)
2023
Children's Hospital Research Institute of Manitoba
2023
University of Alberta
2011-2021
Institute of Virology of the Slovak Academy of Sciences
2015-2020
University Hospital of Basel
2014
University of Washington
2007-2013
Seattle University
2013
Institute of Neuroimmunology of the Slovak Academy of Sciences
2009
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in expression levels could be important susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, transcriptionally independent truncated isoform ACE2, designate deltaACE2 (dACE2). We demonstrate that dACE2,...
To date, only monoclonal antibodies have been shown to be effective for outpatients with COVID-19. Interferon lambda-1 is a type III interferon involved in innate antiviral responses activity against respiratory pathogens. We aimed investigate the safety and efficacy of peginterferon lambda treatment mild-to-moderate COVID-19.In this double-blind, placebo-controlled trial, laboratory-confirmed COVID-19 were randomly assigned single subcutaneous injection 180 μg or placebo within 7 days...
With the first reports on coronavirus disease 2019 (COVID-19), which is caused by novel severe acute respiratory syndrome 2 (SARS-CoV-2), scientific community working in field of type III IFNs (IFN-λ) realized that this class could play an important role and other emerging viral infections. In Viewpoint, we present our opinion benefits potential limitations using IFN-λ to prevent, limit, treat these dangerous
<h3>Background & aims</h3> Inflammatory bowel diseases (IBD) are affected by dietary factors, including nondigestible carbohydrates (fibers), which fermented colonic microbes. Fibers overall beneficial, but not all fibers alike, and some patients with IBD report intolerance to fiber consumption. Given reproducible evidence of reduced fiber-fermenting microbes in IBD, we hypothesized that remain intact select can then bind host cell receptors, subsequently promoting gut inflammation....
Although a cure for HCV is on the near horizon, emerging drug cocktails will be expensive, associated with side-effects and resistance making global vaccine an urgent priority given estimated high incidence of infection around world. Due to highly heterogeneous nature HCV, effective which could elicit broadly cross-neutralizing antibodies has represented major challenge. In this study, we tested presence in human volunteers who were immunized recombinant glycoproteins gpE1/gpE2 derived from...
Abstract Objective Peripheral blood cells (PBMCs) from some patients with systemic sclerosis (SSc) express an interferon‐α (IFNα) signature. The aim of this study was to determine whether SSc patient sera could induce IFNα and induction associated specific autoantibodies and/or clinical features the disease. Methods containing against either topoisomerase I (anti–topo I; n = 12), nucleolar protein (ANoA; or centromeric (ACA; 13) were cultured a HeLa nuclear extract normal PBMCs. In...
Abstract Neuropsychiatric disease in systemic lupus erythematosus (NPSLE) is a poorly understood, but potentially fatal, manifestation. A pathogenetic role for autoantibodies suspected, the mechanism unclear. Since immune complexes SLE can stimulate IFN-α and there strong evidence humans mice that cause neuropsychiatric manifestations, we asked whether NPSLE patient serum and/or cerebrospinal fluid (CSF) contain abnormally high IFN-α-inducing activity. In bioassay containing plasmacytoid...
Almost all humans with homozygous deficiency of C1q develop systemic lupus erythematosus (SLE). The precise cellular mechanism(s) by which prevents the development SLE remains unclear. In this study, we tested role in regulation IFN-α induced immune complexes (ICs) vitro, as well consequences lack vivo. Our experiments revealed that preferentially promotes binding ICs to monocytes rather than plasmacytoid dendritic cells, but inhibition was not due induction inhibitory soluble factors....
Influenza is a major cause of morbidity and mortality in immunosuppressed persons, vaccination often confers insufficient protection. IL-28B, member the interferon (IFN)-λ family, has variable expression due to single nucleotide polymorphisms (SNPs). While type-I IFNs are well known modulate adaptive immunity, impact IL-28B on B- T-cell vaccine responses unclear. Here we demonstrate that presence TG/GG genotype (rs8099917, minor-allele) was associated with increased seroconversion following...
Feedback mechanisms between interferons α and λ (IFNs) may be affected by single nucleotide polymorphisms (SNP) in interleukin 28B (IL-28B; IFN-λ3) promoter region influence cytomegalovirus (CMV) replication.We associated IL-28B SNPs with the risk of CMV replication after transplantation. Next, we examined effect genotypes on IL-28B, IFN-stimulated gene (ISG) expression, human foreskin fibroblast (HFF) peripheral blood mononuclear cells (PBMCs).Transplant recipients an SNP (rs8099917) had...
Type III interferons (IFN-lambdas(λ)) are important cytokines that inhibit viruses and modulate immune responses by acting through a unique IFN-λR1/IL-10RB heterodimeric receptor. Until now, the primary antiviral function of IFN-λs has been proposed to be at anatomical barrier sites. Here, we examine regulation IFN-λR1 expression measure downstream effects IFN-λ3 stimulation in human blood cells, compared with lung or liver epithelial cells. directly bound upregulated IFN-stimulated gene...
Abstract Interferons induced early after SARS-CoV-2 infection are crucial for shaping immunity and preventing severe COVID-19. We previously demonstrated that injection of pegylated interferon-lambda accelerated viral clearance in COVID-19 patients (NCT04354259). To determine if the decline is mediated by enhanced immunity, we assess vivo responses to single cell RNA sequencing measure SARS-CoV-2-specific T antibody between placebo interferon-lambda-treated patients. Here show treatment...
The interaction of neutrophils with T cells has been the subject debate and controversies. Previous studies have suggested that may suppress or activate cells. Despite these studies, between remained a largely unexplored field. Here, based on our RNA sequencing (RNA-seq) analysis, we found differential transcriptional functional profiling depending CD4 T-cell count HIV-infected individual. In particular, identified in healthy individuals express surface Galectin-9 (Gal-9), which is...
Immune complexes (ICs) play a pivotal role in causing inflammation systemic lupus erythematosus (SLE). Yet, it remains unclear what the dominant blood cell type(s) and inflammation-related gene programs stimulated by ICs are. To address these questions, we exposed normal human PBMCs or CD14(+) isolated monocytes to SLE presence absence of C1q performed microarray analysis other tests for activation. By analysis, identified genes pathways regulated that are both type I IFN dependent...
Objective Plasmacytoid dendritic cells (PDCs) produce high concentrations of interferon‐α (IFNα) following exposure to immune complexes containing nucleic acids. We previously reported that serum from healthy donors inhibits IFNα production by PDCs in response systemic lupus erythematosus (SLE) complexes, and inhibition is mediated, part, IgG. IgG the major component intravenous immunoglobulin well known exert antiinflammatory properties. Although suppression inflammation sialylated...
To investigate pathogenic mechanisms of primary sclerosing cholangitis (PSC), biliary cirrhosis (PBC), and autoimmune hepatitis (AIH), serum levels 26 chemokines cytokines were determined compared with patients chronic C or in healthy controls. The chemokine eotaxin-3 (E3; CCL26), which recruits eosinophils to sites inflammation, was found be highly elevated all PSC, PBC, AIH HCV Eotaxin-1 (E1; CCL11), another eosinophil-specific chemokine, PSC but reduced PBC AIH, while the...
Therapeutic options against pathogenic human coronaviruses remain limited. In a recent clinical trial, we demonstrated the therapeutic efficacy of pegylated-IFN-λ in COVID-19 outpatients. However, emergence variants that have potential to evade IFN-mediated antiviral responses raises concerns regarding continued this approach. work, compared sensitivity SARS-CoV-2 and MERS-CoV IFN-λ treatment vitro explored combination therapy with other FDA-authorized or approved agents. We observed...
Mixed cryoglobulinemia is the most common extrahepatic disease manifestation of chronic hepatitis C virus (HCV) infection, where immunoglobulins precipitate at low temperatures and cause symptoms such as vasculitis, glomerulonephritis arthralgia. HCV-associated also strongly linked with development B cell non-Hodgkin lymphoma. Abnormal function in HCV infections can lead to formation cryoglobulin complexes that usually comprise monoclonal rheumatoid factor HCV-specific immune complexes. The...
A comprehensive understanding of signaling pathways requires detailed knowledge regarding ligand-receptor interaction. This article describes two fast and reliable point-by-point protocols enzyme-linked immunosorbent assays (ELISAs) for the investigation interactions: direct interaction assay (LRA) competition LRA. As a case study, ELISA based analysis between different lambda interferons (IFNLs) alpha subunit their receptor (IL28RA) is presented: LRA used determination dissociation...
ABSTRACT Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in expression levels could be important susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, primate-specific isoform , designate deltaACE2 (dACE2) . We demonstrate that dACE2 but not is ISG....
Background. Influenza vaccine immunogenicity is suboptimal in immunocompromised patients. However, there are limited data on the interplay of T- and B- cell responses to vaccination with simultaneous immunosuppression. Methods. We collected peripheral blood mononuclear cells from transplant recipients before 1 month after seasonal influenza vaccination. Before vaccination, H1N1-specific B-cell activation were quantified flow cytometry. also developed a mathematical model using markers...