- Antimicrobial Resistance in Staphylococcus
- Streptococcal Infections and Treatments
- Immune Response and Inflammation
- Neonatal and Maternal Infections
- Immune cells in cancer
- Inflammasome and immune disorders
- Bacterial biofilms and quorum sensing
- Antimicrobial Peptides and Activities
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Mast cells and histamine
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Infective Endocarditis Diagnosis and Management
- Characterization and Applications of Magnetic Nanoparticles
- Clostridium difficile and Clostridium perfringens research
- Tryptophan and brain disorders
- Nanoparticle-Based Drug Delivery
- Genetic Associations and Epidemiology
- Inflammation biomarkers and pathways
- T-cell and B-cell Immunology
- Asthma and respiratory diseases
- Cancer, Hypoxia, and Metabolism
- Bacterial Identification and Susceptibility Testing
- Epigenetics and DNA Methylation
- Food Allergy and Anaphylaxis Research
Helmholtz Centre for Infection Research
2016-2025
Technische Universität Braunschweig
2024
Zoological Institute
2024
Biology of Infection
2011
German Center for Infection Research
2005
Immunoresponsive gene 1 ( Irg1 ) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify as the coding for an enzyme producing itaconic acid (also known methylenesuccinic acid) through decarboxylation of cis -aconitate, a tricarboxylic cycle intermediate. Using gain-and-loss-of-function approach both mouse and human immune cells, found expression levels correlating with amounts acid, metabolite previously...
REVIEW article Front. Immunol., 11 January 2013Sec. Molecular Innate Immunity Volume 3 - 2012 | https://doi.org/10.3389/fimmu.2012.00420
Regulatory cells, such as regulatory T cells (Tregs), B (Bregs), and myeloid-derived suppressor (MDSCs), play a crucial role in preserving immune tolerance controlling responses during infections to prevent excessive activation. However, pathogens have developed strategies hijack these decrease the overall effectiveness of response persist within host. Consequently, therapeutic targeting immunosuppressive mechanisms infection can reinvigorate improve outcome. The suppressive are not only...
Osteomyelitis is a difficult-to-eradicate bone infection typically caused by Staphylococcus aureus. In this study, we investigated the in vivo transcriptional adaptation of S. aureus during infection. To end, determined transcriptome acute (day 7) and chronic 28) phases experimental murine osteomyelitis using RNA sequencing (RNA-Seq). We identified total 180 genes significantly more highly expressed or than under vitro growth conditions. These encoded proteins involved gluconeogenesis,...
In this study, we investigated the interactions of Staphylococcus aureus with mast cells, which are multifunctional sentinels lining surfaces body. We found that bone marrow-derived murine cells (BMMC) exerted a powerful phagocytosis-independent antimicrobial activity against S. aureus. Both release extracellular traps as well discharge compounds were mechanisms used by BMMC to kill This was accompanied secretion mediators such TNF-α involved in recruitment effector cells. Interestingly,...
Abstract The rise of antibiotic resistance calls for alternative strategies to treat bacterial infections. One attractive strategy is directly target virulence factors with anti-virulence drugs. expression traits by pathogens is, however, not constitutive but rather induced the level stress encountered within host. Here we use dual RNA sequencing (RNA-seq) show that intrinsic variability in host greatly affects pathogen's transcriptome vivo . Through analysis transcriptional profiles and...
Macrophages provide the first line of defense against invading pathogens. The aim this study was to determine role macrophages during infection with group A streptococci (Streptococcus pyogenes) in mice. Here, we report that resident can efficiently take up and kill S. pyogenes vivo infection, as demonstrated by immunofluorescence electron microscopy, well colony counts. To evaluate contribution resolution experimental pyogenes, compared susceptibility BALB/c mice rendered macrophage...
ABSTRACT The complex response of murine macrophages to infection with Streptococcus pyogenes was investigated at the level gene expression a high-density oligomer microarray. More than 400 genes were identified as being differentially regulated. Many up-regulated encode molecules involved in immune and inflammation, transcription, signaling, apoptosis, cell cycle, electron transport, adhesion. Of particular interest up-regulation proinflammatory cytokines, typical classically activated (M1...
Macrophages are crucial components of the host defence against Streptococcus pyogenes. Here, we demonstrate ability S. pyogenes to kill macrophages through activation an inflammatory programmed cell death pathway. exposed exhibited extensive cytoplasmic vacuolization, cellular and organelle swelling rupture plasma membrane typical oncosis. The cytotoxic effect on is mediated by streptococcal cytolysins streptolysin S O does not require bacterial internalization. pyogenes-induced was affected...
We have previously reported that myeloid-derived suppressor cells (MDSC), which are a heterogeneous population of immunosuppressive immature myeloid cells, expanded during chronic Staphylococcus aureus infection and promoted bacterial persistence by inhibiting effector T cells. Two major MDSC subsets, including monocytic granulocytic MDSC, been described to date. Here, we identified new subset (Eo-MDSC) in S. aureus-infected mice phenotypically resembles eosinophils. Eo-MDSC exhibit...
Staphylococcus aureus is an important cause of chronic infections resulting from the failure host to eliminate pathogen. Effective S. clearance requires CD4+ T cell-mediated immunity. We previously showed that myeloid-derived suppressor cells (MDSC) expand during staphylococcal and support infection chronicity by inhibiting cell responses. The aim this study was elucidate mechanisms underlying suppressive effect exerted MDSC on infection. It well known activated undergo metabolic...
Despite advances in antimicrobial and anti-inflammatory treatment, inflammation its consequences remain a major challenge the field of medicine. Inflammatory reactions can lead to life-threatening conditions such as septic shock, while chronic has potential worsen condition body tissues ultimately significant impairment their functionality. Although central nervous system long been considered immune privileged peripheral responses, recent research shown that strong responses periphery also...
Streptococcus pyogenes is generally an extracellular pathogen that can survive and persist within the host by circumventing defense mechanisms. To achieve this, S. has developed a number of strategies to circumvent immune system (e.g., virulence factors directed prevent phagocytosis). By use murine model skin infection, it was shown survival phagocytic cells constitutes additional strategy used evade defenses disseminate. Viable microorganisms were isolated from mouse after in vitro or...
Streptococcus pyogenes is one of the most frequent human pathogens. Recent studies have identified dendritic cells (DCs) as important contributors to host defense against S. pyogenes. The objective this study was identify receptors involved in immune recognition by DCs. To determine whether Toll-like (TLRs) were DC sensing pyogenes, we evaluated response bone marrow-derived DCs obtained from mice deficient MyD88, an adapter molecule used almost all TLRs, following stimulation. Despite fact...
Streptococcus pyogenes is a significant human pathogen that can cause life-threatening invasive infections. Understanding the mechanism of disease crucial to development more effective therapies. In this report, we explored role PGE(2), an arachidonic acid metabolite, and its rate-limiting enzyme cyclooxygenase 2 (COX-2) in pathogenesis severe S. We found COX-2 expression levels tissue biopsies from pyogenes-infected patients, as well experimentally infected mice, strongly correlated with...
Neutrophil extracellular trap (NET) formation is a significant innate immune defense mechanism against microbial infection that complements other neutrophil functions including phagocytosis and degranulation of antimicrobial peptides. NETs are decondensed chromatin structures in which components (histones, peptides proteases) deployed mediate immobilization microbes. Here we describe an effect iron chelation on the phenotype NET formation. Iron-chelating agent desferrioxamine (DFO) showed...
Mast cells (MCs) are important sentinels of the host defence against invading pathogens. We previously reported that Staphylococcus aureus evaded extracellular antimicrobial activities MCs by promoting its internalization within these via β1 integrins. Here, we investigated molecular mechanisms governing this process. found S. responded to mediators released up-regulating expression α-hemolysin (Hla), fibronectin-binding protein A and several regulatory systems. also induced up-regulation...
Abstract Isoniazid‐filled Fe 2 O 3 hollow nanospheres (INH@Fe , diameter <30 nm, 48 wt % INH‐load) are prepared for the first time and suggested tuberculosis therapy. After dextran‐functionalization, INH@Fe @DEX nanocontainers show strong activity against Mycobacterium (M.tb.) M.tb.‐infected macrophages. The can be considered as “Trojan horses” efficient, active uptake into both macrophages even mycobacterial cells.