A5008363586- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Carbohydrate Chemistry and Synthesis
- Immune Response and Inflammation
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Biochemical and Molecular Research
- Antibiotic Resistance in Bacteria
- Pneumonia and Respiratory Infections
- Escherichia coli research studies
- Bacteriophages and microbial interactions
- Pneumocystis jirovecii pneumonia detection and treatment
- RNA and protein synthesis mechanisms
- Infectious Diseases and Tuberculosis
- Helicobacter pylori-related gastroenterology studies
- Immunodeficiency and Autoimmune Disorders
- Bacterial Genetics and Biotechnology
- Clostridium difficile and Clostridium perfringens research
- Enzyme Production and Characterization
- Salmonella and Campylobacter epidemiology
- Polysaccharides and Plant Cell Walls
- Viral gastroenteritis research and epidemiology
- Infectious Diseases and Mycology
- Phagocytosis and Immune Regulation
Université de Toulouse
2014-2024
Institut de Pharmacologie et de Biologie Structurale
2014-2024
Université Toulouse III - Paul Sabatier
2014-2024
Centre National de la Recherche Scientifique
2014-2024
University of Birmingham
2003-2016
Laboratoire de Biotechnologie de l'Environnement
2013
Centre National pour la Recherche Scientifique et Technique (CNRST)
2009
Newcastle University
2002-2003
Gut microbes affect immunotherapy The unleashing of antitumor T cell responses has ushered in a new era cancer treatment. Although these therapies can cause dramatic tumor regressions some patients, many patients inexplicably see no benefit. Mice have been used two studies to investigate what might be happening. Specific members the gut microbiota influence efficacy this type (see Perspective by Snyder et al. ). Vétizou found that optimal anticytotoxic lymphocyte antigen blockade required...
Interactions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to infects DCs through ligation DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) mannose-capped lipoarabinomannan (ManLAM) inhibits binding bacilli lectin, suggesting ManLAM might be DC-SIGN ligand. In present study, we investigated molecular basis by LAM....
Lipoarabinomannans (LAM) and lipomannans (LM) are integral parts of the mycobacterial cell wall recognized by cells involved in innate immune response have been found to modulate cytokine response. Typically, mannosylated LAM from pathogenic mycobacteria reported be anti-inflammatory, whereas phosphoinositol-substituted nonpathogenic species proinflammatory molecules. In this study, we show that LM several species, including Mycobacterium chelonae, kansasii, bovis bacillus Calmette-Guérin,...
Pathogenic mycobacteria have the ability to persist in phagocytic cells and suppress immune system. The glycolipid lipoarabinomannan (LAM), particular its mannose cap, has been shown inhibit phagolysosome fusion induce immunosuppressive IL-10 production via interaction with receptor or DC-SIGN. Hence, current paradigm is that cap of LAM a crucial factor mycobacterial virulence. However, above studies were performed purified LAM, never live bacteria. Here we evaluate biological properties...
Mycobacterium tuberculosis mannose-capped lipoarabinomannan inhibits the release of proinflammatory cytokines by LPS-stimulated human dendritic cells (DCs) via targeting C-type lectin receptor DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN). With aim mimicking bioactive supramolecular structure lipoarabinomannan, we designed and synthesized a set poly(phosphorhydrazone) dendrimers grafted with mannose units, called mannodendrimers, that differed size number...
Significance For many years, the development of adjuvants—compounds that boost immunogenicity vaccines—has been an empirical process. Adjuvants inducing a strong humoral immunity are available, but adjuvants directing robust cellular immune responses still needed. Recently, C-type lectin receptor Mincle was found to elicit such on recognition microbial glycolipids, thereby providing basis for rational design new adjuvants. Here we used multidisciplinary approach, combining chemical...
Significance To secure their colonization and survival, pathogens have evolved tactics to undermine host immune responses. Most particularly, Mycobacterium tuberculosis inhibits the activation of macrophages, one whose roles is recognize kill invading microorganisms. Here, we used a library M. mutants infect macrophages uncover molecular mechanisms by which pathogen modulates function these cells. We found that produces cell envelope glycolipids are antagonists macrophage receptor, named...
Mycobacterium tuberculosis possesses a variety of immunomodulatory factors that influence the host immune response. When bacillus encounters its target cell, outermost components cell envelope are first to interact. Mycobacteria, including M. tuberculosis, surrounded by loosely attached capsule is mainly composed proteins and polysaccharides. Although chemical composition relatively well studied, biological function only poorly understood. The aim this study was further assess functional...
Mycobacterium tuberculosis lipomannans (LMs) modulate the host innate immune response. The total fraction of bovis BCG LM was shown both to induce macrophage activation and pro-inflammatory cytokines through Toll-like receptor 2 (TLR2) inhibit cytokine production by lipopolysaccharide (LPS)-activated macrophages a TLR2-independent pathway. activity attributed tri- tetra-acylated forms but not mono- di-acylated ones. Here, we further characterize negative activities M. on primary murine...
The C-type lectin dendritic cell−specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) mediates the innate immune recognition of microbial carbohydrates. We investigated function this molecule in host response to pathogens vivo, by generating mouse lines lacking DC-SIGN homologues SIGNR1, SIGNR3, and SIGNR5. Resistance Mycobacterium tuberculosis was impaired only SIGNR3-deficient animals. SIGNR3 expressed lung phagocytes during infection, interacted with M. bacilli...
A posttranslational protein O-mannosylation process resembling that found in fungi and animals has been reported the major human pathogen Mycobacterium tuberculosis (Mtb) related actinobacteria. However, role incidence of this process, which is essential eukaryotes, have never explored Mtb. We thus analyzed impact interrupting nonpathogenic saprophyte smegmatis Mtb by inactivating respective putative mannosyl transferase genes Msmeg_5447 Rv1002c. Loss both mutant strains was unambiguously...
Significance Tuberculosis (TB) is an immunopathology, mostly of the lung, due to overexuberant immune response bacterial pathogen Mycobacterium tuberculosis . Here, we demonstrate in vitro and vivo that dendritic cell (DC) immunoreceptor (DCIR), a C-type lectin receptor expressed by DCs, modulates immunity TB sustaining type I IFN signaling DCs. These findings were generalized beyond TB, model antigen-presentation assay unrelated M. , suggesting they may extend other pathologies, such as...
Abstract An estimated one-third of tuberculosis (TB) cases go undiagnosed or unreported. Sputum samples, widely used for TB diagnosis, are inefficient at detecting infection in children and paucibacillary patients. Indeed, developing point-of-care biomarker-based diagnostics that not sputum-based is a major priority the WHO. Here, proof-of-concept study, we tested whether pulmonary can be detected by analyzing patient exhaled breath condensate (EBC) samples. We find presence Mycobacterium...
Lipoarabinomannans are major mycobacterial antigens capable of modulating the host immune response; however, molecular basis underlying diversity their immunological properties remain an open question. In this study a new extraction and purification approach was successfully applied to isolate ManLAMs (lipoarabinomannans with mannosyl extensions) from bacillus Calmette Guérin leading obtention two types namely parietal cellular. Structurally, they were found differ by percentage...
Interactions between dendritic cells and Mycobacterium tuberculosis, the aetiological agent of tuberculosis in humans, are thought to be central anti-mycobacterial immunity. We have previously shown that M. binds human monocyte-derived mostly through C-type lectin DC-SIGN (dendritic-cell-specific intercellular molecule-3-grabbing non-integrin)/CD209, we suggested may discriminate mycobacterial species recognition mannose-capping residues on lipoglycan lipoarabinomannan bacterial envelope....
Summary Corynebacterium glutamicum and Mycobacterium tuberculosis share a similar cell wall architecture, the availability of their genome sequences has enabled utilization C. as model for identification study of, otherwise essential, mycobacterial genes involved in lipomannan (LM) lipoarabinomannan (LAM) biosynthesis. We selected putative glycosyltransferase‐Rv2174 from M. deleted its orthologue NCgl2093 . This resulted formation novel truncated (Cg‐t‐LM) complete ablation LM/LAM...
Changes in the cell envelope composition of mycobacteria cause major changes cytokine profiles infected antigen presenting cells. We describe here modulation inflammatory responses by Mycobacterium abscessus, an emerging pathogen cystic fibrosis. M. abscessus is able to switch from a smooth (S) rough (R) morphotype loss surface glycopeptidolipid. R variants are associated with severe clinical forms and 'hyper-proinflammatory' response ex vivo models. Using partitioning components we found...
Mycobacterium abscessus lung infections remain difficult to treat. Recent studies have recognized the power of new combinations antibiotics, such as bedaquiline and imipenem, although in vitro data questioned this combination. We report that efficacy bedaquiline-imipenem combination treatment relies essentially on activity a C3HeB/FeJ mice model infection with rough variant M. . The addition imipenem contributed clearing spleen.
Autophagy is an important innate immune defense mechanism that controls Mycobacterium tuberculosis (Mtb) growth inside macrophages. machinery targets Mtb-containing phagosomes via xenophagy after damage to the phagosomal membrane due Type VII secretion system Esx-1 or LC3-associated phagocytosis without damage. Conversely, Mtb restricts autophagy-related pathways production of various bacterial protein factors. Although lipids are known play strategic functions in pathogenesis, their role...