A5070409333- Pneumonia and Respiratory Infections
- Legionella and Acanthamoeba research
- Immune Response and Inflammation
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Extracellular vesicles in disease
- Pneumocystis jirovecii pneumonia detection and treatment
- Respiratory Support and Mechanisms
- Asthma and respiratory diseases
- MicroRNA in disease regulation
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cancer-related molecular mechanisms research
- Respiratory viral infections research
- RNA modifications and cancer
- Antimicrobial Peptides and Activities
- interferon and immune responses
- Bacterial Infections and Vaccines
- Neonatal Respiratory Health Research
- Pediatric health and respiratory diseases
- NF-κB Signaling Pathways
- Pulmonary Hypertension Research and Treatments
- Inflammasome and immune disorders
- Antibiotic Resistance in Bacteria
- Heme Oxygenase-1 and Carbon Monoxide
- Antimicrobial Resistance in Staphylococcus
German Center for Lung Research
2016-2025
Loewe Center for Synthetic Microbiology
2019-2025
Philipps University of Marburg
2016-2025
Universities of Giessen and Marburg Lung Center
2016-2025
German Center for Infection Research
2020-2025
Institut für Lungenforschung
2014-2024
Justus-Liebig-Universität Gießen
2002-2024
Uniwersytecki Szpital Dziecięcy
2024
Children's Clinical University Hospital
2024
Ludwig-Maximilians-Universität München
2021-2024
Influenza A viruses (IAV) and influenza B (IBV) cause significant morbidity mortality during seasonal outbreaks. Cleavage of the viral surface glycoprotein hemagglutinin (HA) by host proteases is a prerequisite for membrane fusion essential virus infectivity. Inhibition relevant provides promising therapeutic approach that may avoid development drug resistance. HA most cleaved at monobasic cleavage site, number have been shown to cleave in vitro . This study demonstrates transmembrane...
Bioactive peptides are key molecules in health and medicine. Deep learning holds a big promise for the discovery design of bioactive peptides. Yet, suitable experimental approaches required to validate candidates high throughput at low cost. Here, we established cell-free protein synthesis (CFPS) pipeline rapid inexpensive production antimicrobial (AMPs) directly from DNA templates. To our platform, used deep thousands AMPs de novo. Using computational methods, prioritized 500 that produced...
Biofilm formation is generally recognized as a bacterial defense mechanism against environmental threats, including antibiotics, bacteriophages, and leukocytes of the human immune system. Here, we show that for pathogen Vibrio cholerae, biofilm not only protective trait but also an aggressive to collectively predate different cells. We find V. cholerae forms biofilms on eukaryotic cell surface using extracellular matrix comprising primarily mannose-sensitive hemagglutinin pili,...
Streptococcus pneumoniae, the major cause of community-acquired pneumonia and bacterial meningitis, has been shown to transiently invade epithelial endothelial cells. Innate immune receptors including Toll-like recognize various pathogens, such as S. by identifying conserved pathogen-associated molecular patterns. Recently, two members a novel class pattern recognition receptors, cytosolic proteins nucleotide-binding oligomerization domain 1 (Nod1)/CARD4 Nod2/CARD15, have found detect cell...
Influenza A virus causes epidemics of respiratory diseases in humans leading to thousands death annually. One its major virulence factors, the non-structural protein 1 (NS1), exhibits interferon-antagonistic properties. While epithelial cells tract are primary targets influenza virus, virus-sensing mechanisms these eventually IFNbeta production incompletely understood. Here we show that infection with NS1-deficient upregulated expression two molecules have been previously implicated sensing...
ABSTRACT Secretion of effector molecules is one the major mechanisms by which intracellular human pathogen Legionella pneumophila interacts with host cells during infection. Specific secretion machineries are responsible for subfraction secreted proteins (soluble supernatant [SSPs]) and production bacterial outer membrane vesicles (OMVs) both contribute to protein composition extracellular milieu this lung pathogen. Here we present comprehensive proteome reference maps SSPs OMVs. Protein...
Abstract Nucleotide-binding oligomerization domain (Nod) proteins serve as intracellular pattern recognition molecules recognizing peptidoglycans. To further examine immune recognition, we used Listeria monocytogenes an organism particularly amenable for studying innate immunity to pathogens. In contrast wild-type L. monocytogenes, the nonpathogenic innocua, or mutants lacking internalin B listeriolysin O, poorly invaded host cells and escaped into cell cytoplasm, respectively, were...
Seroepidemiological and animal studies, as well demonstration of viable bacteria in atherosclerotic plaques, have linked Chlamydophila pneumoniae infection to development chronic vascular lesions coronary heart disease. Inflammation immune responses are dependent on host recognition invading pathogens. The recently identified cytosolic Nod proteins candidates for intracellular bacteria, such the obligate chlamydia. In present study, mechanisms endothelial cell activation by C . via were...
Abstract Different NOD-like receptors, including NLRP1, NLRP3, and NLRC4, as well the recently identified HIN-200 protein, AIM2, form multiprotein complexes called inflammasomes, which mediate caspase-1–dependent processing of pro-IL-1β. Listeria monocytogenes is an intracellular pathogen that actively phagocytosed by monocytes/macrophages subsequently escapes from phagosome into host cell cytosol, depending on its pore-forming toxin listeriolysin O (LLO). In this study, we demonstrate human...
IL-17-producing CD8+ (Tc17) cells are enriched in active lesions of patients with multiple sclerosis (MS), suggesting a role the pathogenesis autoimmunity. Here we show that amelioration MS by dimethyl fumarate (DMF), mechanistically elusive drug, associates suppression Tc17 cells. DMF treatment results reduced frequency Tc17, contrary to Th17 cells, and decreased ratio regulators RORC-to-TBX21, along shift towards cytotoxic T lymphocyte gene expression signature from patients....
Abstract Activated caspase-1 and caspase-11 induce inflammatory cell death in a process termed pyroptosis. Here we show that Prostaglandin E 2 (PGE ) inhibits caspase-11-dependent pyroptosis murine human macrophages. PGE suppreses expression macrophages the airways of mice with allergic inflammation. Remarkably, caspase-11-deficient are strongly resistant to developing experimental airway inflammation, where is known be protective. Expression elevated lung wild type Blocking production...
Endothelial hyperpermeability induced by inflammatory mediators is a hallmark of sepsis and adult respiratory distress syndrome. Increased levels the regulatory peptide adrenomedullin (ADM) have been found in patients with systemic response. We analyzed effect ADM on permeability cultured human umbilical vein endothelial cell (HUVEC) porcine pulmonary artery monolayers. dose-dependently reduced hydrogen peroxide (H 2 O ), thrombin, Escherichia coli hemolysin. Moreover, pretreatment blocked H...
Legionella pneumophila, a Gram-negative facultative intracellular bacterium, causes severe pneumonia (Legionnaires' disease). Type I interferons (IFNs) were so far associated with antiviral immunity, but recent studies also indicated role of these cytokines in immune responses against (intracellular) bacteria. Here we show that wild-type L. pneumophila and flagellin-deficient Legionella, not lacking functional type IV secretion system Dot/Icm, or heat-inactivated induced IFNβ expression...
Objective: Acute respiratory failure is a significant complication of severe pneumococcal pneumonia. In mouse model, we observed early-onset lung microvascular leakage after pulmonary infection with Streptococcus pneumoniae, and hypothesized that the important virulence factor pneumolysin may be direct causative agent. Design: Controlled, in vivo, ex vitro laboratory study. Setting: Laboratory. Subjects: Female mice, 8–12 wks old. Interventions: Ventilated blood-free perfused murine lungs...
Abstract In mice, different alleles of the mNAIP5 (murine neuronal apoptosis inhibitory protein-5)/mBirc1e gene determine whether macrophages restrict or support intracellular replication Legionella pneumophila, and a mouse is resistant (moderately) susceptible to infection. mice strains, nucleotide-binding oligomerization domain (Nod)-like receptor (NLR) family member mNAIP5/mBirc1e, as well NLR protein mIpaf ICE protease-activating factor), are involved in recognition flagellin restriction...
Activation of the endothelium by oxidized low-density lipoprotein (oxLDL) has been implicated in development atherosclerosis. Histone modifications impact on transcriptional activity state genes. We tested hypothesis that oxLDL-induced inflammatory gene expression is regulated histone and experienced effect statins these alterations.OxLDL-related interleukin-8 (IL-8) monocyte-chemoattractant protein-1 (MCP-1) secretion endothelial cells was reduced but enhanced deacetylase inhibitors. OxLDL...
Objectives: Community-acquired pneumonia is a very common infectious disease associated with significant morbidity and mortality. Streptococcus pneumoniae the predominant pathogen in this disease, pneumococcal resistance to multiple antibiotics increasing. The recently purified bacteriophage endolysin Cpl-1 rapidly specifically kills pneumococci on contact. aim of study was determine therapeutic potential mouse model severe pneumonia. Design: Controlled, vivo laboratory study. Subjects:...
Patients with stable COPD show improvements in exercise capacity and muscular function after the application of whole body vibration. We aimed to evaluate whether this modality added conventional physiotherapy exacerbated hospitalised patients would be safe improve quality life. 49 were randomized (1:1) undergo alone or addition The primary endpoint was between-group difference 6-minute walking test (day discharge – day admission). Secondary assessments included chair rising test, life,...
The formation and release of outer membrane vesicles (OMVs) is a phenomenon Gram-negative bacteria. This includes Legionella pneumophila (L. pneumophila), causative agent severe pneumonia. Upon its transmission into the lung, L. primarily infects replicates within macrophages. Here, we analyzed influence OMVs on To this end, differentiated THP-1 cells were incubated with increasing doses OMVs, leading to TLR2-dependent classical activation macrophages pro-inflammatory cytokines. Inhibition...