A5004326415- Immune Response and Inflammation
- Gallbladder and Bile Duct Disorders
- Liver Diseases and Immunity
- NF-κB Signaling Pathways
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cytokine Signaling Pathways and Interactions
- Gut microbiota and health
- Inflammasome and immune disorders
- interferon and immune responses
- Immunotherapy and Immune Responses
- Antimicrobial Resistance in Staphylococcus
- Immune Cell Function and Interaction
- Histone Deacetylase Inhibitors Research
- Pediatric Hepatobiliary Diseases and Treatments
- Infective Endocarditis Diagnosis and Management
- Mycobacterium research and diagnosis
- Diphtheria, Corynebacterium, and Tetanus
- Viral Infections and Vectors
- Bacterial Identification and Susceptibility Testing
- Diverticular Disease and Complications
- Helicobacter pylori-related gastroenterology studies
- Diet and metabolism studies
- Immune cells in cancer
- Rabies epidemiology and control
- Toxin Mechanisms and Immunotoxins
CS Diagnostics
2024
Heidelberg University
2009-2023
Institute of Medical Microbiology and Hygiene
2007-2020
Medizinisches Versorgungszentrum Prof. Mathey, Prof. Schofer
2020
University Hospital Heidelberg
2013-2018
Deutsche Forschungsgemeinschaft
2016
Chirurgische Universitätsklinik Heidelberg
2015
Heidelberg University
2011
DKFZ-ZMBH Alliance
2002
German Cancer Research Center
2002
Post-translational modifications of histone proteins are major mechanisms that modify chromatin structure and regulate gene expression in eukaryotes. Activation acetyltransferases or inhibition deacetylases (HDACs) is generally believed to allow assume a more open state, permitting transcriptional activity. We report here the surprising observation treatment murine dendritic cells with HDAC inhibitors trichostatin A (TSA) suberoylanilide hydroxamic acid (SAHA) non-apoptotic concentrations...
Objective: Lethal sepsis occurs when an excessive inflammatory response evolves that cannot be controlled by physiologic anti-inflammatory mechanisms, such as the recently described cholinergic pathway. Here we studied whether pathway can activated pharmacologic cholinesterase inhibition in vivo. Design: Prospective, randomized laboratory investigation used established murine model. Setting: Research a university hospital. Subjects: Female C57BL/6 mice. Interventions: Sepsis mice was induced...
Extracellular vesicles (EVs) are released from nearly all mammalian cells and different EV populations have been described. Microvesicles represent large EVs (LEVs) the cellular surface, while exosomes small (SEVs) an intracellular compartment. As it is likely that stimuli promote release of distinct populations, we analyzed human lymphocytes considering respective (activation vs. apoptosis induction). We could clearly separate two namely SEVs (average diameter <200nm) LEVs (diameter range...
Sepsis is a major cause of mortality in hospitalized patients worldwide, with lethality rates ranging from 30 to 70 %. caused by variety different pathogens, and rapid diagnosis outstanding importance, as early adequate antimicrobial therapy correlates positive clinical outcome. In recent years, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) fingerprinting has become powerful tool microbiological diagnostics. The direct identification...
In LPS-treated macrophages, activation of STAT3 is considered to be crucial for terminating the production inflammatory cytokines. By analyzing role MAPK-activated protein kinase (MK) 2 and MK3 LPS-induced in present study provides evidence that MK2 response LPS because it prevents from impeding IFNβ gene expression. Accordingly, expression down-regulated MK2-deficient macrophages can reconstituted by additional ablation MK2/3−/− macrophages. This contrast IL-10 expression, which essentially...
Abstract Background Comprehensive pathogen genomic surveillance represents a powerful tool to complement and advance precision vaccinology. The emergence of the Alpha variant in December 2020 resulting efforts track spread this other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concern led an expansion sequencing activities Germany. Methods At Robert Koch Institute (RKI), German National Public Health, we established Integrated Molecular Surveillance for SARS-CoV-2...
Airway epithelial cells regulate immune reactivity of local dendritic (DCs), thus contributing to microenvironment homeostasis. In this study, we set out identify factors that mediate regulatory interaction. We show tracheal secrete soluble downregulate TNF-α and IL-12p40 secretion by bone marrow-derived DCs but upregulate IL-10 arginase-1. Size exclusion chromatography identified small secreted molecules having high modulatory activity on DCs. observed airway constitutively release the...
Bacterial components are recognized by the immune system through activation of inflammasome, eventually causing processing proinflammatory cytokine interleukin-1? (IL-1?), a pleiotropic and one most important mediators inflammation, protease caspase-1. Synthesis precursor protein into its bioactive form tightly regulated, given that disturbed control IL-1? release can cause severe autoinflammatory diseases or contribute to cancer development. We show bacterial Pasteurella multocida toxin...
The aim of this study was to determine the antibiotic susceptibility profiles bacteria in bile samples and analyze clinical relevance findings as only limited information about risk factors for elevated frequence bacterial fungal strains routinely collected has been described so far. A prospective cohort at a tertiary care center conducted. Seven hundred forty-four patients underwent 1401 endoscopic retrograde cholangiographies (ERCs) indicated by liver transplantation (427/1401), primary...
Abstract Background Heart failure with preserved ejection fraction (HFpEF) is associated systemic inflammation, obesity, metabolic syndrome, and gut microbiome changes. Increased trimethylamine-N-oxide (TMAO) levels are predictive for mortality in HFpEF. The TMAO precursor trimethylamine (TMA) synthesized by the intestinal microbiome, crosses barrier metabolized to hepatic flavin-containing monooxygenases (FMO). intricate interactions of alterations relation HFpEF manifestation progression...
<b>Background and study aims:</b> To determine the importance of bacteriobilia fungibilia in patients with endoscopic treatment biliary complications after orthotopic liver transplantation (OLT). <b>Patients methods:</b> In a prospective at tertiary center, 213 underwent 857 retrograde cholangiographies (ERCs) OLT. Findings first ERC were: anastomotic stricture 24.4 %, nonanastomotic 18.3 leakage 11.3 gallstones 4.7 %. <b>Results:</b> Bile samples from showed Gram-positive bacterial isolates...
Histone deacetylase (HDAC) inhibitors (HDACi) are clinically approved anticancer drugs that have important immune-modulatory properties. We report the surprising finding HDACi promote LPS-induced IL-1β processing and secretion in human murine dendritic cells macrophages. HDACi/LPS-induced maturation kinetics differed completely from those observed upon inflammasome activation. Moreover, this pathway of was dependent on caspase-8 but independent components NACHT, LRR, PYD domains-containing...
Summary Synthetic oligodeoxynucleotides containing unmethylated CpG sequences (CpG‐ODNs) stimulate Toll‐like receptor‐9 (TLR‐9), thereby activating innate immunity. Stimulatory CpG‐ODNs have been shown to be valuable in modifying immune responses allergy, infection and cancer. Recently, it has reported that the stimulation of TLR‐9 by endogenous DNA might contribute pathogenesis autoimmune diseases. We here report identification a suppressive, guanosine‐rich ODN (G‐ODN) inhibited activation...
IL-12 is a crucial cytokine for dendritic cell-mediated induction of Th 1 cell differentiation. TLR ligands induce to differing extents. Stimulation cells allowed the differentiation three groups TLRs; potency decreased in order TLR7/9, TLR3/4, and TLR1/2/6 stimulation. The MAPK, PI3K, IRF (IFN regulatory factor) signaling pathways could be ruled out cause differences IL-12p40 induction. However, we observed that stimulation with different resulted striking kinetics NF-kappaB activation. LPS...
Candidiasis is commonly observed in patients with primary sclerosing cholangitis (PSC), but the clinical risk factors associated its presence have not been fully investigated. In this study, we aimed to analyse incidence, factors, and transplantation-free survival (PSC) persistent biliary candidiasis. We retrospectively analysed diagnosed PSC who were admitted our department during 2002 2012. One-hundred fifty whose bile cultures tested for fungal species selected, their laboratory...
The significance of bacterial RNA recognition for initiating innate immune responses against invading pathogens has only recently started to be elucidated. Bacterial is an important trigger inflammasome activation, resulting in caspase-1-dependent cleavage pro-IL-1β into the active form. It was reported previously that prolonged treatment with IFN-γ can inhibit IL-1β production at level both transcription and Nlrp3 activation NO-dependent manner. As a result delayed kinetics NO generation...
Summary Background A recent genome‐wide association study identified the FUT 2 secretor status and genotype defined by single‐nucleotide polymorphism rs601338 as potential genetic risk factor in primary sclerosing cholangitis ( PSC ), which significantly influences biliary bacterial composition. Aim To determine impact of rs601338‐ on frequency infections, development dominant stenosis liver‐transplantation‐free survival patients with PSC. Methods Cohort 215 treated at our tertiary care...
Abstract Classical STAT1 activation in response to TLR agonists occurs by phosphorylation of the Y701 and S727 residues through autocrine type I IFN signaling p38 MAPK signaling, respectively. In this study, we report that TLR9 agonist CpG DNA induced Ifn-β mRNA, as well downstream IFN-dependent genes, a MyD88-dependent manner mouse myeloid dendritic cells. This pathway was required for maximal TNF IL-6 secretion, expression cell surface costimulatory molecules. By contrast, neither A- nor...
Antigen presenting cells (APCs) regulate the balance of our immune response towards microbes. Whereas immunogenic APCs boost inflammation and activate lymphocytes, highly plastic can switch into a tolerogenic/suppressive phenotype that dampens resolves response. Thereby initially mediated seems to prime while strength activation determines grade suppressive phenotype. Recently we showed pathogen recognition receptor-mediated pro-inflammatory cytokines reprogram differentiating human blood...
Hyporesponsiveness of human lamina propria immune cells to microbial and nutritional antigens represents one important feature intestinal homeostasis. It is at least partially mediated by low expression the innate response receptors CD11b, CD14, CD16 as well cystine-glutamate transporter xCT on these cells. Milieu-specific mechanisms leading down-regulation circulating monocytes, precursor resident macrophages, are mostly unknown.Here, we addressed question whether short chain fatty acid...
The bacterial protein toxin Pasteurella multocida (PMT) mediates RANKL-independent osteoclast differentiation. Although these osteoclasts are smaller, their resorptive activity is high which helps in efficient destruction of nasal turbinate bones pigs. proteome bone marrow-derived macrophages differentiated into with either RANKL or PMT was analysed. results were verified by characterizing the metabolic using Seahorse analysis, a translation assay, immunoblots, real-time PCR as well flow...