A5044213528- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Cellular Mechanics and Interactions
- Blood Coagulation and Thrombosis Mechanisms
- Glycosylation and Glycoproteins Research
- Erythrocyte Function and Pathophysiology
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Cell Adhesion Molecules Research
- Antibiotic Resistance in Bacteria
- Calcium signaling and nucleotide metabolism
- Cellular transport and secretion
- Pneumocystis jirovecii pneumonia detection and treatment
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Biochemical and Molecular Research
- Heparin-Induced Thrombocytopenia and Thrombosis
- Bacteriophages and microbial interactions
- Cancer therapeutics and mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Phagocytosis and Immune Regulation
University of Basel
2015-2025
Génétique Moléculaire Génomique Microbiologie
2022
Addenbrooke's Hospital
2006
Nanyang Technological University
2006
Imperial College London
2006
National University of Singapore
2006
Wellcome Centre for Cell-Matrix Research
2005
Cornell University
2005
University of British Columbia
2005
Phenex Pharmaceuticals (Germany)
2004
Mycobacteria are intracellular pathogens that can invade and survive within host macrophages, thereby creating a major health problem worldwide. The molecular mechanisms involved in mycobacterial entry still poorly characterized. Here we report cholesterol is essential for uptake of mycobacteria by macrophages. Cholesterol accumulated at the site entry, depleting plasma membrane specifically inhibited uptake. also mediated phagosomal association TACO, coat protein prevents degradation...
Pathogenic mycobacteria resist lysosomal delivery after uptake into macrophages, allowing them to survive intracellularly. We found that the eukaryotic-like serine/threonine protein kinase G from pathogenic was secreted within macrophage phagosomes, inhibiting phagosome-lysosome fusion and mediating intracellular survival of mycobacteria. Inactivation by gene disruption or chemical inhibition resulted in localization mycobacterial cell death infected macrophages. Besides identifying a target...
Abstract Dendritic cells, in contrast to B lymphocytes, must be able efficiently internalize a diverse array of antigens for processing and loading onto major histo‐compatibility complex (MHC) class II molecules. Here we characterize the mannose receptor pathway dendritic cells show that receptor‐mediated uptake results ∼ 100‐fold more efficient presentation T as compared internalized via fluid phase. Immunocytochemistry well subcellular fractionation revealed localization MHC molecules...
Chemotherapeutic options to treat tuberculosis are severely restricted by the intrinsic resistance of Mycobacterium majority clinically applied antibiotics. Such is partially provided low permeability their unique cell envelope. Here we describe a complementary system that coordinates drugs have penetrated envelope, allowing mycobacteria tolerate diverse classes antibiotics inhibit cytoplasmic targets. This depends on whiB7 , gene pathogenic shares with Streptomyces phylogenetically related...
The oligomeric complex formed by major histocompatibility (MHC) class II alpha and beta chains invariant chain (Ii) assembles in the endoplasmic reticulum is then transported via Golgi to compartments of endocytic pathway. When Ii alone expressed CV1 cells it sorted endosomes. cytoplasmic tail has been found be essential for targeting these compartments. In order characterize further signals responsible endosomal targeting, we have deleted various segments tail. mutants were transiently...
An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unknown. We found that myHsp70, in addition enhancing antigen delivery human dendritic cells, signaled through CCR5 chemokine receptor, promoting cell aggregation, synapse formation between cells and T generation...
Significance Group 3 innate lymphoid cells (ILC3s) play decisive roles in mammalian physiology including tissue repair, development, and immune regulation. So far, the functions of ILC3s adult system have been mainly linked to their capacity release cytokines response microbial or inflammatory signals. The results presented here show that activated can alter outcome adaptive responses by directly stimulating CD4 + T cells. Indeed, IL-1β–activated express costimulatory molecules induce...
The pathogenicity of mycobacteria such as Mycobacterium tuberculosis is closely associated with their capacity to survive within host macrophages. A crucial virulence factor for intracellular mycobacterial survival protein kinase G (PknG), a eukaryotic-like serine/threonine expressed by pathogenic that blocks the degradation in lysosomes. Inhibition PknG highly selective low-molecular-weight inhibitor AX20017 results transfer lysosomes and killing mycobacteria. Here, we report 2.4 Å x-ray...
Mounting an immune response against foreign, extracellular material requires that this be internalized by antigen presenting cells, processed to peptide fragments and then displayed on the cell surface for recognition T receptor helper cells. Such peptides, derived from antigens are generally presented cells in association with Major Histocompatibility Complex (MHC) class II molecules. Recent work has identified subcompartments of endosomal/lysosomal system appear important sites generation...
The intracellular transport and location of major histocompatibility complex (MHC) class II molecules associated invariant chain (Ii) were investigated in a human melanoma cell line. In contrast to the molecules, which remain stable for greater than 4 h after synthesis, Ii is proteolytically processed within 2 h. During or shortly synthesis NH2-terminal cytoplasmic membrane-spanning segment some cleaved off; during transport, membrane integrated from its COOH terminus distinct steps...
Coronin 1 is a member of the coronin protein family specifically expressed in leukocytes and accumulates at sites rearrangements F-actin cytoskeleton. Here, we describe that molecules are coiled coil-mediated homotrimeric complexes, which associate with plasma membrane cytoskeleton via two distinct domains. Association was mediated by trimerization stretch positively charged residues within linker region between N-terminal, WD repeat-containing domain C-terminal coil. In contrast, neither...
ABSTRACT While in most rod-shaped bacteria, morphology is based on MreB-like proteins that form an actin-like cytoskeletal scaffold for cell wall biosynthesis, the factors determine more flexible rod-like shape actinobacteria such as Mycobacterium species are unknown. Here we show a smegmatis protein homologous to eubacterial DivIVA-like proteins, including M. tuberculosis antigen 84 (Ag84), localized symmetrically centers of peptidoglycan biosynthesis at poles and septa. Controlled gene...