A5061995723- Antimicrobial Resistance in Staphylococcus
- Biochemical and Structural Characterization
- Bacterial biofilms and quorum sensing
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- Pediatric health and respiratory diseases
- Respiratory and Cough-Related Research
- Dermatology and Skin Diseases
- Fungal Infections and Studies
- Cardiac and Coronary Surgery Techniques
- Cardiac Valve Diseases and Treatments
- Immunodeficiency and Autoimmune Disorders
- Antifungal resistance and susceptibility
- Autophagy in Disease and Therapy
- Antimicrobial Peptides and Activities
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Aortic Disease and Treatment Approaches
- Monoclonal and Polyclonal Antibodies Research
- Mosquito-borne diseases and control
- Vibrio bacteria research studies
- Eosinophilic Esophagitis
- Escherichia coli research studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Gut microbiota and health
Amsterdam University Medical Centers
2023-2024
University of Amsterdam
2023-2024
University of Tübingen
2020-2024
German Center for Infection Research
2023-2024
Czech Academy of Sciences, Institute of Microbiology
2024
Utrecht University
1998-2021
University Medical Center Utrecht
2017-2021
Heidelberg University
2021
University Hospital Heidelberg
2021
University of Toronto
2018-2019
Linking protein misfolding and innate immunity Multiple immune sensors undergo rapid assembly into large complexes known as signalosomes. This is an essential step during cellular responses to microbes danger signals. How this process regulated avoid accumulation of potentially toxic aggregates remains poorly understood. Abdel-Nour et al. identified a pathway, dependent on heme-regulated inhibitor, eukaryotic initiation factor 2α, activating transcription 4, heat shock B8, which controls the...
Langerhans cells are a subset of dendritic residing in the epidermis human skin. As such, they key mediators immune regulation and have emerged as prime targets for novel transcutaneous cancer vaccines. Importantly, induction protective T cell immunity by these vaccines requires efficient specific delivery both tumor-associated antigens adjuvants. uniquely express Langerin (CD207), an endocytic C-type lectin receptor. Here, we report discovery specific, glycomimetic ligand employing...
The bacterium Staphylococcus aureus is an important cause of skin infections and also associated with the occurrence severity eczema. Langerhans cells (LCs), a specific subset immune cells, participate in response to S. , but it yet unclear how LCs recognize . Therefore, we investigated molecular mechanism underlying interaction between We identified that wall teichoic acid, abundant polymer on surface, recognized by langerin, receptor unique LCs. This allows discriminate from other related...
Bacterial microbiota permanently colonize host barrier sites such as the gastrointestinal tract. Select members of contribute to antibody-based homeostasis and defense by inducing local systemic antibody responses, respectively. However, molecular mechanisms underlying selection these immunologically-relevant are still unknown. Barrier-resident antigen-presenting cells (APCs) critical initiate immune responses upon bacterial invasion. Furthermore, APCs sample environment across intact...
The gut microbiome contributes to inflammatory bowel disease (IBD), in which bacteria can be present within the epithelium. Epithelial barrier function is decreased IBD, and dysfunctional epithelial mitochondria endoplasmic reticulum (ER) stress have been individually associated with IBD. We therefore hypothesized that combination of ER mitochondrial stresses significantly disrupt function. Here, we treated human colonic biopsies, colonoids, cells an uncoupler oxidative phosphorylation,...
Staphylococcus aureus is the leading cause of skin and soft tissue infections. It remains incompletely understood how skin-resident immune cells respond to invading S. contribute an effective response. Langerhans (LCs), only professional antigen-presenting cell type in epidermis, sense through their pattern-recognition receptor langerin, triggering a proinflammatory Langerin recognizes β-1,4-linked N-acetylglucosamine (β1,4-GlcNAc) but not α-1,4-linked GlcNAc (α1,4-GlcNAc) modifications,...
Staphylococcus aureus is a common skin commensal but also associated with various and soft tissue pathologies. Upon invasion, S. detected by resident innate immune cells through pattern-recognition receptors (PRRs), although comprehensive understanding of the specific molecular interactions lacking. Recently, we demonstrated that PRR langerin (CD207) on epidermal Langerhans senses conserved β-1,4-linked N-acetylglucosamine (GlcNAc) modification wall teichoic acid (WTA), thereby increasing...
Abstract Background The cell envelope of Staphylococcus aureus contains 2 major secondary wall glycopolymers: capsular polysaccharide (CP) and teichoic acid (WTA). Both CP WTA are attached to the play distinct roles in S. colonization, pathogenesis, bacterial evasion host immune defenses. We aimed investigate whether interferes with WTA-mediated properties. Methods Strains natural heterogeneous expression CP, strains homogeneous high expression, CP-deficient were compared regarding...
Respiratory mucosal host defense relies on the production of secretory IgA (sIgA) antibodies, but we currently lack a fundamental understanding how sIgA is induced by contact with microbes and such immune responses may vary between humans. Defense nasal barrier through critical to protect from infection maintain homeostasis microbiome, which influences respiratory disorders hosts opportunistic pathogens.We applied IgA-seq analysis microbiota samples male female healthy volunteers, identify...
The success of Staphylococcus aureus as a major cause for endovascular infections depends on effective interactions with blood-vessel walls. We have previously shown that S. uses its wall teichoic acid (WTA), surface glycopolymer, to attach endothelial cells. However, the WTA receptor remained unknown. show here oxidized low-density lipoprotein 1 (LOX-1) interacts and permits binding human Purified LOX-1 bound isolated WTA. Ectopic expression led increased wild type but not WTA-deficient...
Langerhans cells are key sentinel of the skin and mucosal lining. They sense microorganisms through their repertoire pattern-recognition receptors to mount direct appropriate immune responses. We recently demonstrated that human interact with Gram-positive pathogen <i>Staphylococcus aureus</i> cell-specific receptor langerin (CD207). It was previously hypothesized two linked single nucleotide polymorphisms (SNPs; N288D K313I) in carbohydrate recognition domain would affect...
Abstract Wall teichoic acids (WTAs) are important components of the cell wall opportunistic Gram‐positive bacterium Staphylococcus aureus . WTAs composed repeating ribitol phosphate (RboP) residues that decorated with d ‐alanine and N ‐acetyl‐ ‐glucosamine (GlcNAc) modifications, in a seemingly random manner. These WTA‐modifications play an role shaping interactions WTA host immune system. Due to structural heterogeneity WTAs, it is impossible isolate pure well‐defined molecules from...
Abstract Staphylococcus aureus is among the leading causes of hospital-acquired infections. Critical to S. biology and pathogenesis are cell wall-anchored glycopolymers wall teichoic acids (WTA). Approximately one-third isolates decorates WTA with a mixture α1,4- β1,4- N -acetylglucosamine (GlcNAc), which requires dedicated glycosyltransferases TarM TarS, respectively. Environmental conditions, such as high salt concentrations, affect abundance ratio β1,4-GlcNAc decorations, thereby...
ABSTRACT Staphylococcus aureus is among the leading causes of hospital-acquired infections. Critical to S. biology and pathogenesis are cell wall-anchored glycopolymers wall teichoic acids (WTA). Approximately one-third isolates decorates WTA with a mixture α1,4- β1,4- N -acetylglucosamine (GlcNAc), which requires dedicated glycosyltransferases TarM TarS, respectively. Environmental conditions, such as high salt concentrations, affect abundance ratio β1,4-GlcNAc decorations, thereby...
Abstract Staphylococcus aureus is a major cause of skin and soft tissue infections aggravator the inflammatory disease atopic dermatitis (AD). Epicutaneous exposure to S. induces Th17 responses through Langerhans cells (LCs), which paradoxically contribute host defense but also AD pathogenesis. The underlying molecular mechanisms association between inflammation are poorly understood. Here, we demonstrate that human LCs directly interact with pattern-recognition receptor langerin (CD207)....
Abstract Background The cell envelope of Staphylococcus aureus contains two major secondary wall glycopolymers: capsular polysaccharide (CP) and teichoic acid (WTA). Both the CP WTA are attached to play distinct roles in S. colonization, pathogenesis, bacterial evasion host immune defenses. Objective We aimed investigate whether interferes with WTA-mediated properties. Methods Strains natural heterogeneous expression CP, strains homogeneous high CP-deficient were compared deficient controls...
Abstract Langerhans cells are a subset of dendritic residing in the epidermis human skin. As such, they key mediators immune regulation and have emerged as prime targets for novel transcutaneous cancer vaccines. Importantly, induction protective T cell immunity by these vaccines requires efficient specific delivery both tumor-associated antigens adjuvants. uniquely express Langerin (CD207), an endocytic C-type lectin receptor. Here, we report discovery specific, glycomimetic ligand employing...