A5002002969- Immune Response and Inflammation
- Inflammation biomarkers and pathways
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Cell Function and Interaction
- Transplantation: Methods and Outcomes
- Immune cells in cancer
- Long-Term Effects of COVID-19
- Sepsis Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- IL-33, ST2, and ILC Pathways
- Neonatal Respiratory Health Research
- Cytomegalovirus and herpesvirus research
- Erythrocyte Function and Pathophysiology
- Cancer-related molecular mechanisms research
- Sirtuins and Resveratrol in Medicine
- Amoebic Infections and Treatments
- Heme Oxygenase-1 and Carbon Monoxide
- interferon and immune responses
- Immune responses and vaccinations
- Tea Polyphenols and Effects
- Gut microbiota and health
- Vibrio bacteria research studies
- Pneumonia and Respiratory Infections
Medical University of Vienna
2014-2025
CeMM Research Center for Molecular Medicine
2013-2022
Austrian Academy of Sciences
2013-2022
University of Veterinary Medicine Vienna
2016-2020
Biology of Infection
2013
Macrophages play a key role in responding to pathogens and initiate an inflammatory response combat microbe multiplication. Deactivation of macrophages facilitates resolution the response. Deactivated are characterized by immunosuppressive phenotype, but lack unique markers that can reliably identify these cells explains poorly defined biological this macrophage subset. We identified lipocalin 2 (LCN2) as both marker deactivated deactivator. show LCN2 attenuated early impaired bacterial...
Objective Liver injury impacts hepatic inflammation in part via Toll-like receptor (TLR) signalling. Triggering expressed on myeloid cells 2 (TREM-2) modulates TLR4-mediated bone marrow (BM)-derived macrophages but its function liver is unknown. Here we hypothesised that the anti-inflammatory effects of TREM-2 TLR signalling may limit injury. Design expression was analysed livers humans with various forms compared control individuals. Acute and chronic models were performed wild type Trem-2...
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 human isolate. In silico modeling revealed how only three Spike mutations maVie16 enhanced interaction with murine ACE2. induced profound pathology BALB/c and C57BL/6 mice, resulting mouse COVID-19 (mCOVID-19) replicated critical aspects disease, including early lymphopenia,...
Pulmonary fibrosis is an incurable disease that manifests with advanced age. Yet, how hematopoietic aging influences immune responses and progression remains unclear. Using heterochronic bone marrow transplant mouse models, we found aged exacerbates lung irrespective of tissue Upon injury, there was increased accumulation monocyte-derived alveolar macrophages (Mo-AMs) driven by cell-intrinsic aging. These Mo-AMs exhibited enhanced profibrotic profile stalled maturation into a homeostatic,...
Lipid metabolism and receptor-mediated signaling are highly intertwined processes that cooperate to fulfill cellular functions safeguard homeostasis. Activation of Toll-like receptors (TLRs) leads a complex response, orchestrating diverse range inflammatory events need be tightly controlled. Here, we identified the GPI-anchored Sphingomyelin Phosphodiesterase, Acid-Like 3B (SMPDL3B) in mass spectrometry screening campaign for membrane proteins co-purifying with TLRs. Deficiency Smpdl3b...
During infections, TLR-mediated responses require tight regulation to allow for pathogen removal, while preventing overwhelming inflammation and immunopathology. The triggering receptor expressed on myeloid cells (TREM)-2 negatively regulates by macrophages impacts phagocytosis, but the function of endogenous TREM-2 during infections is poorly understood. We investigated TREM-2's role in regulating TLR4-mediated studying wild-type TREM-2-/- mice challenged with LPS found dampen early...
Phagocytosis and inflammation within the lungs is crucial for host defense during bacterial pneumonia. Triggering receptor expressed on myeloid cells (TREM)-2 was proposed to negatively regulate TLR-mediated responses enhance phagocytosis by macrophages, but role of TREM-2 in respiratory tract infections unknown. Here, we established presence alveolar macrophages (AM) explored function innate immune response pneumococcal infection vivo. Unexpectedly, found Trem-2−/− AM display augmented...
As ACE2 is the critical SARS-CoV-2 receptor, we hypothesized that aerosol administration of clinical grade soluble human recombinant (APN01) will neutralize in airways, limit spread infection lung, and mitigate lung damage caused by deregulated signaling renin-angiotensin (RAS) Kinin pathways. Here, after demonstrating vitro neutralization APN01, obtaining preliminary evidence its tolerability preventive efficacy a mouse model, pursued development an formulation. prerequisite to trial,...
Rationale Lung transplantation is the ultimate treatment option for patients with end-stage respiratory diseases but bears highest mortality rate among all solid organ transplantations due to chronic lung allograft dysfunction (CLAD). The mechanisms leading CLAD remain elusive an insufficient understanding of complex post-transplant adaptation processes. Objectives To better understand these processes after and investigate their association future changes in function. Methods We performed...
Community-acquired pneumonia (CAP), often caused by Streptococcus pneumoniae, poses a significant global health challenge, especially among high-risk populations. This study investigates the temporal dynamics of pulmonary gene expression during S. pneumoniae-induced using murine model to elucidate host-pathogen interactions and identify potential biomarkers disease severity. Using bulk RNA sequencing, we analyzed lung tissues at early (1h, 8h) acute infection (2d, 3d), as well...
Patho-mechanistic origins and disease dynamics of ulcerative colitis are still poorly understood. The actin-crosslinker Filamin A (FLNA) impacts cellular responses through interaction with cytosolic proteins. FLNA exists in two forms that differ only one amino acid: genome-encoded FLNAQ FLNAR - generated by post-transcriptional A-to-I editing. is edited fibroblasts, smooth muscle- endothelial cells the colon. We identified editing status as a key determinant severity. was highest healthy...
Clearance of invading pathogens is essential to preventing overwhelming inflammation and sepsis that are symptomatic bacterial peritonitis. Macrophages participate in this innate immune response by engulfing digesting pathogens, a process called phagocytosis. Oxidized phospholipids (OxPL) danger-associated molecular patterns (DAMPs) generated infection can prevent the phagocytic clearance bacteria. We investigated mechanism underlying OxPL action macrophages. Exposure induced alterations...
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has been causing the COVID-19 pandemic since December 2019, with over 600 million infected persons worldwide and six deaths. We investigated anti-viral effects of polyphenolic green tea ingredients synthetic resveratrol analogue 3,3',4,4',5,5'-hexahydroxy-trans-stilbene (HHS), a compound antioxidant, antitumor anti-HIV properties. In TCID50 assay, four out nine constituents showed minor to modest cell protective effects,...
Sepsis is a life-threatening condition characterized by uncontrolled systemic inflammation and coagulation, leading to multiorgan failure. Therapeutic options prevent sepsis-associated immunopathology remain scarce. Here, we established mouse model of long-lasting disease tolerance during severe sepsis, manifested diminished immunothrombosis organ damage in spite high pathogen burden. We found that both neutrophils B cells emerged as key regulators tissue integrity. Enduring changes the...
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 expressed on myeloid cells 2 (Trem2 -/-) were protected from LCMV-induced hepatitis showed improved control despite comparable virus-specific T cell responses. Non-hematopoietic...
Abstract To develop a universal strategy to block SARS-CoV-2 cellular entry and infection represents central aim for effective COVID-19 therapy. The growing impact of emerging variants concern increases the urgency development interventions. Since ACE2 is critical receptor all tested bind ACE2, some even at much increased affinity (see accompanying paper), we hypothesized that aerosol administration clinical grade soluble human recombinant (APN01) will neutralize in airways, limit spread...
Summary 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 human isolate. In silico modelling revealed how Spike mutations enhanced interaction with murine ACE2. MaVie16 induced profound pathology BALB/c and C57BL/6 mice resulting mouse COVID-19 ( mCOVID-19 ) replicated critical aspects disease, including early lymphopenia,...
In Figure 7, C and D, the term AG-1478