Sylvia Knapp

Sylvia Knapp
Medical University of Vienna | MedUni Vienna · Laboratory of Infection Biology

MD, PhD

About

171
Publications
17,650
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6,163
Citations
Additional affiliations
January 2006 - present
Austrian Academy of Sciences (OeAW)
Position
  • PI

Publications

Publications (171)
Article
Full-text available
As ACE2 is the critical SARS-CoV-2 receptor, we hypothesized that aerosol administration of clinical grade soluble human recombinant ACE2 (APN01) will neutralize SARS-CoV-2 in the airways, limit spread of infection in the lung, and mitigate lung damage caused by deregulated signaling in the renin-angiotensin (RAS) and Kinin pathways. Here, after de...
Article
Full-text available
The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to both reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is, therefore, paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here, we report that all SARS-CoV-2 variants analyzed, incl...
Article
Full-text available
Environmental microbial triggers shape the development and functionality of the immune system. Alveolar macrophages (AMs), tissue-resident macrophages of the lungs, are in constant and direct contact with inhaled particles and microbes. Such exposures likely impact AM reactivity to subsequent challenges by immunological imprinting mechanisms referr...
Article
Background & Aims Due to the complex multifactorial origin and an incomplete understanding of the underlying disease mechanisms, progression of non-alcoholic fatty liver disease (NAFLD) into advanced non-alcoholic steatohepatitis (NASH) and liver fibrosis is predicted to become the primary indication for liver transplantation. Hence, there is an un...
Article
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Background The virome of lung transplant recipients (LTRs) under immunosuppressive therapy is dominated by non-pathogenic Anelloviridae and further includes several pathogenic viruses such as Herpesviruses or respiratory viruses. It is unclear whether the donor-derived virome in the transplanted lung influences recipient virome dynamics in other bo...
Preprint
FOXP3 ⁺ regulatory T cells (Tregs) are key for immune homeostasis. Tregs are a heterogenous population, however mechanisms regulating their transition from naïve to effector Tregs (eTregs) are poorly understood. Here, we reveal a novel role for nuclear receptor corepressor 1 (NCOR1) in effector Tregs (eTregs). NCOR1 represses an effector signature...
Preprint
Sepsis is a life-threatening condition characterized by uncontrolled systemic inflammation and coagulation, leading to multi-organ failure. Therapeutic options to prevent sepsis-associated immunopathology remain scarce. Here, we established a model of long-lasting disease tolerance during severe sepsis, manifested by diminished immunothrombosis and...
Article
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In silico modelling revealed how only three Spike mutations of maVie16 enhanced interaction with murine ACE2. MaVie16 induced profound pathology in BALB/c and C57BL/6 mice and the resulting mouse COVID-19 (mCOVID-19) replicated critical aspects of human disease, including early lymphopenia, pulmonary immune cell infiltration, pneumonia and specific...
Article
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T helper (Th) 17 cells are not only key in controlling infections mediated by extracellular bacteria and fungi but are also triggering autoimmune responses. Th17 cells comprise heterogeneous subsets, some with pathogenic functions. They can cease to secrete their hallmark cytokine IL-17A and even convert to other T helper lineages, a process known...
Article
Tissue-resident macrophages are of vital importance as they preserve tissue homeostasis in all mammalian organs. Nevertheless, appropriate cell culture models are still limited. Here, we propose a novel culture model to study and expand murine primary alveolar macrophages (AMs), the tissue-resident macrophages of the lung, in vitro over several mon...
Preprint
Full-text available
To develop a universal strategy to block SARS-CoV-2 cellular entry and infection represents a central aim for effective COVID-19 therapy. The growing impact of emerging variants of concern increases the urgency for development of effective interventions. Since ACE2 is the critical SARS-CoV-2 receptor and all tested variants bind to ACE2, some even...
Preprint
Full-text available
Despite tremendous progress in the understanding of COVID-19, mechanistic insight into immunological, disease-driving factors remains limited. We generated maVie16 , a mouse-adapted SARS-CoV-2, by serial passaging of a human isolate. In silico modelling revealed how Spike mutations of maVie16 enhanced interaction with murine ACE2. MaVie16 induced p...
Article
Rationale Lung transplantation is the ultimate treatment option for patients with end-stage respiratory diseases but bears the highest mortality rate among all solid organ transplantations due to chronic lung allograft dysfunction (CLAD). The mechanisms leading to CLAD remain elusive due to insufficient understanding of the complex post-transplant...
Article
Full-text available
Lipocalin 2 (LCN2) is a secreted glycoprotein with roles in multiple biological processes. It contributes to host defense by interference with bacterial iron uptake and exerts immunomodulatory functions in various diseases. Here, we aimed to characterize the function of LCN2 in lung macrophages and dendritic cells (DCs) using Lcn2-/- mice. Transcri...
Article
Purpose Allograft adaptation after lung transplantation is a multi-factor process. We hypothesized that early adaptation can influence the risk of matrix remodeling and CLAD development by shaping the inflammatory state of the lung environment. In a longitudinal study, we followed a defined patient cohort in year 1 p.t. and detected ordered cell co...
Article
Full-text available
Background In contrast to theirclearly defined rolesin allergic diseases, the physiologic functions of Immunoglobulin E antibodies (IgEs) and mast cells (MCs) remainenigmatic. Recent research supports the toxin hypothesis,showing thatMCs and IgE‐related type 2 immune responses can enhance host defense against certain noxious substances, including h...
Article
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Obesity-induced white adipose tissue (WAT) hypertrophy is associated with elevated adipose tissue macrophage (ATM) content. Overexpression of the triggering receptor expressed on myeloid cells 2 (TREM2) reportedly increases adiposity, worsening health. Paradoxically, using insulin resistance, elevated fat mass and hypercholesterolemia as hallmarks...
Preprint
Tissue-resident macrophages are of vital importance as they preserve tissue homeostasis in all mammalian organs. Nevertheless, appropriate cell culture models are still limited. Here, we propose a novel culture model to study and expand murine primary alveolar macrophages (AMs), the tissue-resident macrophages of the lung, in vitro over several mon...
Article
Full-text available
Objectifying donor lung quality is difficult and currently there is no consensus. Several donor scoring systems have been proposed in recent years. They all lack large‐scale external validation and widespread acceptance. A retrospective evaluation of 2201 donor lungs offered to the lung transplant program at the Medical University of Vienna between...
Article
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Objective: Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer usually arising on a background of chronic liver injury involving inflammatory and hepatic regenerative processes. The triggering receptor expressed on myeloid cells 2 (TREM-2) is predominantly expressed in hepatic non-parenchymal cells and inhibits Toll-like receptor s...
Article
Allergies are considered to represent mal-directed type 2 immune responses against mostly innocuous exogenous compounds. Immunoglobulin E (IgE) antibodies are a characteristic feature of allergies and mediate hypersensitivity against allergens through activation of effector cells, particularly mast cells (MCs). Although the physiological functions...
Article
Purpose Spirometric lung function is one of the central clinical parameters to assess allograft function after lung transplantation (LTX). Reduction in FEV1 can be the result of infections, rejections episodes and most importantly development of CLAD. Currently, there is no means to predict short-term changes in lung function after LTX. Methods Br...
Article
Purpose The pulmonary microbiome after lung transplantation has recently come into the focus of research. Especially, host-microbiome interactions are thought to be an important factor in graft-related immunological processes. In lung transplantation, temporal changes of the pulmonary microbiome have not yet been elucidated. Methods In a total coh...
Article
Full-text available
The differentiation of naïve CD4+ T cells into T helper (Th) subsets is key for a functional immune response and has to be tightly controlled by transcriptional and epigenetic processes. However, the function of cofactors that connect gene-specific transcription factors with repressive chromatin-modifying enzymes in Th cells is yet unknown. Here we...
Article
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Forkhead box protein P3+ (FOXP3+) regulatory T cells (Treg cells) play a key role in maintaining tolerance and immune homeostasis. Here, we report that a T cell-specific deletion of the transcription factor MAZR (also known as PATZ1) leads to an increased frequency of Treg cells, while enforced MAZR expression impairs Treg cell differentiation. Fur...
Article
Rheumatoid Arthritis (RA) represents a chronic T cell-mediated inflammatory autoimmune disease. Studies have shown that epigenetic mechanisms contribute to the pathogenesis of RA. Histone deacetylases (HDACs) represent one important group of epigenetic regulators. However, the role of individual HDAC members for the pathogenesis of arthritis is sti...
Article
Red blood cells (RBCs) comprise 84% of our body's cells and have the essential function of transporting oxygen from the lungs to all organs. The daily production rate of RBCs is enormous and the pathways mediating this process are quite complex. One important aspect hereby is the synthesis of hemoglobin and heme, the iron-containing prosthetic grou...
Article
Introduction Blood platelets are increasingly recognized as modulators of leukocyte effector functions in various pathologies including acute lung injury (ALI). ALI is a life-threatening disease, caused by damage to the alveolar epi- and endothelium. Excessive accumulation of leukocytes leads to severe lung inflammation, resulting in impaired lung...
Article
Lung development and function arises from the interactions between diverse cell types and lineages. Using single-cell RNA sequencing (RNA-seq), we characterize the cellular composition of the lung during development and identify vast dynamics in cell composition and their molecular characteristics. Analyzing 818 ligand-receptor interaction pairs wi...
Conference Paper
Background Despite enormous efforts to develop new therapeutic strategies for treatment of rheumatoid arthritis (RA), the large number of non responding patients to currently available drugs underlies the unmet need to identify new therapeutic targets. Objectives Certain CD4⁺T cell subsets, especially Th17 cells, have been shown to be major driver...
Conference Paper
Introduction Despite enormous efforts to develop new therapeutic strategies for treatment of rheumatoid arthritis (RA), the large number of non responding patients to currently available drugs underlies the unmet need to identify new therapeutic targets. Certain CD4⁺T cells have been shown to be major drivers of inflammation in patients with RA. Th...
Article
Full-text available
Objective Liver injury impacts hepatic inflammation in part via Toll-like receptor (TLR) signalling. Triggering receptor expressed on myeloid cells 2 (TREM-2) modulates TLR4-mediated inflammation in bone marrow (BM)-derived macrophages but its function in liver injury is unknown. Here we hypothesised that the anti-inflammatory effects of TREM-2 on...
Article
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Lipid metabolism is increasingly being appreciated to affect immunoregulation, inflammation and pathology. In this study we found that mice infected with lymphocytic choriomeningitis virus (LCMV) exhibit global perturbations of circulating serum lipids. Mice lacking the lipid-sensing surface receptor triggering receptor expressed on myeloid cells 2...
Article
Heme is a vital, iron-containing prosthetic molecule present in a variety of proteins, of which hemoglobin is the most abundant. While the reactivity afforded by its central iron ion is essential for many cellular processes, it renders heme a potentially damaging molecule upon its release from hemeproteins, as it can catalyze the generation of reac...
Data
Data S1. Methods. Fig. S1. Genotyping data of myeloid and airway epithelial TF‐deficient mice. Fig. S2. Macrophage recruitment into the lung 8 h after acid‐induced acute lung injury (ALI). Fig. S3. Myeloid TF does not influence leukocyte recruitment during sterile peritonitis. Fig. S4. No significant changes in IL‐12 and IL‐1β levels between my...
Conference Paper
Background Autoreactive T cells have been shown to play a major role in Rheumatoid Arthritis, which drive the inflammatory process leading to an irreversible destruction of the joints. Gene transcription and regulation of proinflammatory cytokine production in T cells is regulated by epigenetic mechanisms. Histone deacetylases (HDACs) modify the ep...
Article
Full-text available
Introduction: Acute lung injury (ALI) is a life-threatening condition characterized by damaged alveolar-capillary structures and activation of inflammatory and hemostatic processes. Tissue factor (TF) represents a crucial link between inflammation and coagulation, as inflammatory mediators induce myeloid TF expression and TF initiates the extrinsi...
Article
Full-text available
From birth onward, the lungs are exposed to the external environment and therefore harbor a complex immunological milieu to protect this organ from damage and infection. We investigated the homeostatic role of the epithelium-derived alarmin interleukin-33 (IL-33) in newborn mice and discovered the immediate upregulation of IL-33 from the first day...
Data
Document S1. Supplemental Experimental Procedures, Figures S1–S7, and Tables S1–S3
Data
From birth onward, the lungs are exposed to the external environment and therefore harbor a complex immunological milieu to protect this organ from damage and infection. We investigated the homeostatic role of the epithelium-derived alarmin interleukin-33 (IL-33) in newborn mice and discovered the immediate upregulation of IL-33 from the first day...
Article
Background and rationale: Diet-related health issues such as non-alcoholic fatty liver disease and cardiovascular disorders are known to have a major inflammatory component. However, the exact pathways linking diet-induced changes e.g. hyperlipidemia, and the ensuing inflammation have remained elusive so far. Main results: We identified biologic...
Article
Hemolysis drives susceptibility to bacterial infections and predicts poor outcome from sepsis. These detrimental effects are commonly considered to be a consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative sepsis model and found that elevated heme levels impaired the control of bacterial proliferation independent...
Article
Full-text available
NF-κB signaling is a central pathway of immunity and integrates signal transduction upon a wide array of inflammatory stimuli. Non-canonical NF-κB signaling is activated by a small subset of TNF family receptors and characterized by NF-κB2/p52 transcriptional activity. The medical relevance of this pathway has recently re-emerged from the discovery...
Article
Introduction: Acute and chronic graft-versus-host-diseases (GVHD) are serious complications after hematopoietic stem cell transplantation (HSCT), impairing survival and quality of life. Since the underlying pathomechanism of GVHD is still poorly understood, we investigated the novel inflammatory marker Pentraxin-3 (PTX3) for its potential role in...
Article
Protecting the integrity of the lung epithelial barrier is essential to ensure respiration and proper oxygenation in patients suffering from various types of lung inflammation. Type I interferon (IFN-I) has been associated with pulmonary epithelial barrier function, however, the mechanisms and involved cell types remain unknown. We aimed to investi...
Article
Full-text available
Scientific Reports 6 : Article number: 23034; 10.1038/srep23034 published online: 14 March 2016 ; updated: 20 May 2016 . The Acknowledgements section and Author Contributions statement were omitted from this Article.
Article
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Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease with limited treatment options. Additionally, the lack of a complete understanding of underlying immunological mechanisms underscores the importance of discovering novel options for therapeutic intervention. Since the PI3K/PTEN pathway in myeloid cells influences their effector funct...
Article
Type I interferons (IFN-Is) are fundamental for antiviral immunity, but their role in bacterial infections is contradictory and incompletely described. Streptococcus pyogenes activates IFN-I production in innate immune cells, and IFN-I receptor 1 (Ifnar1)-deficient mice are highly susceptible to S. pyogenes infection. Here we report that IFN-I sign...
Article
Full-text available
Proper development of the immune system is an intricate process dependent on many factors, including an intact DNA damage response. The DNA double-strand break signaling kinase ATM and its cofactor NBS1 are required during T cell development and for the maintenance of genomic stability. The role of a second ATM cofactor, ATMIN (also known as ASCIZ)...
Article
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The Ki-1 antigen (CD30) is an established therapeutic target in patients with Hodgkin's lymphoma and anaplastic large cell lymphoma. We have recently shown that CD30 is expressed abundantly in the cytoplasm of neoplastic mast cells (MC) in patients with advanced systemic mastocytosis (SM). In the current study, we asked whether CD30 is expressed on...
Article
Full-text available
Lipid metabolism and receptor-mediated signaling are highly intertwined processes that cooperate to fulfill cellular functions and safeguard cellular homeostasis. Activation of Toll-like receptors (TLRs) leads to a complex cellular response, orchestrating a diverse range of inflammatory events that need to be tightly controlled. Here, we identified...
Article
Full-text available
A large subset of mammalian imprinted genes show extra-embryonic lineage (EXEL) specific imprinted expression that is restricted to placental trophectoderm lineages and to visceral yolk sac endoderm (ysE). Isolated ysE provides a homogenous in vivo model of a mid-gestation extra-embryonic tissue to examine the mechanism of EXEL-specific imprinted g...