A5059968213- Escherichia coli research studies
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Bacterial Genetics and Biotechnology
- Immune Cell Function and Interaction
- Gut microbiota and health
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Helicobacter pylori-related gastroenterology studies
- Protein Kinase Regulation and GTPase Signaling
- NF-κB Signaling Pathways
- Bacteriophages and microbial interactions
- Infections and bacterial resistance
- Neonatal Health and Biochemistry
- Cell Adhesion Molecules Research
- CRISPR and Genetic Engineering
- Yersinia bacterium, plague, ectoparasites research
- Heat shock proteins research
- Biochemical and Structural Characterization
- Vibrio bacteria research studies
- RNA Interference and Gene Delivery
- Diet, Metabolism, and Disease
- 3D Printing in Biomedical Research
- Endoplasmic Reticulum Stress and Disease
- Adenosine and Purinergic Signaling
Institut Cochin
2001-2023
Université Paris Cité
2014-2023
Inserm
2014-2023
Centre National de la Recherche Scientifique
1998-2023
Sorbonne Paris Cité
2015-2019
Délégation Paris 5
2014-2019
Canadian Nautical Research Society
2016
University of Basel
2007-2015
Centre de Gestion Scientifique
2015
Descartes (Belgium)
2014
TOR (Target of Rapamycin) is a highly conserved protein kinase and central controller cell growth. found in two functionally structurally distinct multiprotein complexes termed complex 1 (TORC1) 2 (TORC2). In the present study, we developed two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) based proteomic strategy to identify new mammalian (mTOR) binding proteins. We report identification Proline-rich Akt substrate (PRAS40) hypothetical Q6MZQ0/FLJ14213/CAE45978 as...
During long-term cystic fibrosis lung infections, Pseudomonas aeruginosa undergoes genetic adaptation resulting in progressively increased persistence and the generation of adaptive colony morphotypes. This includes small variants (SCVs), auto-aggregative, hyper-adherent cells whose appearance correlates with poor function infection. The SCV morphotype is strongly linked to elevated levels cyclic-di-GMP, a ubiquitous bacterial second messenger that regulates transition between motile...
During infection by invasive bacteria, epithelial cells contribute to innate immunity via the local secretion of inflammatory cytokines. These are directly produced infected or uninfected bystanders connexin-dependent cell-cell communication. However, cellular pathways underlying this process remain largely unknown. Here we perform a genome-wide RNA interference screen and identify TIFA TRAF6 as central players Shigella flexneri Salmonella typhimurium-induced interleukin-8 expression. We...
The commensal bacteria that make up the gut microbiota impact health of their host on multiple levels. In particular, interactions taking place between microbe-associated molecule patterns (MAMPs) and pattern recognition receptors (PRRs), expressed by intestinal epithelial cells (IECs), are crucial for maintaining homeostasis. While numerous studies showed TLRs NLRs involved in control homeostasis bacteria, role additional innate immune remains unclear. Here, we seek novel MAMP-PRR...
The anaerobic bacterium Fusobacterium nucleatum is significantly associated with human colorectal cancer (CRC) and considered a significant contributor to the disease. mechanisms underlying promotion of intestinal tumor formation by F. have only been partially uncovered. Here, we showed that releases metabolite into microenvironment strongly activates NF-κB in epithelial cells via ALPK1/TIFA/TRAF6 pathway. Furthermore, released molecule had biological characteristics ADP-heptose. We observed...
The serine/threonine kinase Akt (also known as protein B) (Akt/PKB) is activated upon T-cell antigen receptor (TCR) engagement or expression of an active form phosphatidylinositide (PI) 3-kinase in T lymphocytes. Here we report that the small GTPase Rac1 implicated this pathway, connecting with lipid kinase. We show Jurkat cells, forms Cdc42, but not Rho, stimulate increase Akt/PKB activity. TCR-induced activation inhibited either by PI inhibitors (LY294002 and wortmannin) overexpression a...
Highlights•TIFA is activated by invasive Shigella in human intestinal epithelial cells•Bacterial production of the metabolite HBP required for TIFA activation•TIFA-activating liberated from bacteria during cytosolic growth•TIFA activation reflects rate and extent bacterial proliferationSummaryIntestinal cells (IECs) act as sentinels incoming pathogens. Cytosol-invasive bacteria, such flexneri, trigger a robust pro-inflammatory nuclear factor κB (NF-κB) response IECs that believed to depend...
The enteroinvasive bacterium Shigella flexneri invades the intestinal epithelium of humans. During infection, several injected effector proteins promote bacterial internalization, and interfere with multiple host cell responses. To obtain a systems-level overview signaling during we analyzed global dynamics protein phosphorylation by liquid chromatography-tandem MS identified hundred undergoing change first hours infection. Functional bioinformatic analysis revealed that they were mostly...
Recognition of the lipopolysaccharide (LPS), a major component outer membrane Gram-negative bacteria, by Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD-2) complex is essential for control bacterial infection. A pro-inflammatory signaling cascade initiated upon binding membrane-associated portion LPS, glycophospholipid Lipid A, coreceptor protein MD-2, which results in protective host innate immune response. However, activation TLR4 LPS may lead to dysregulated response...
Abstract The human leukocyte surface Ag CD38 was recently identified as a nicotinamide adenine dinucleotide (NAD)(+)-glycohydrolase ecto-enzyme, degrading NAD into and ADP-ribose. We show here that expression of is increased in the Jurkat T cell line after treatment with agents augment intracellular cAMP, permeant cAMP analogue dibutyryl-cAMP (db-cAMP), also PMA, which activates protein kinase C. Treatment PBL cells db-cAMP or submitogenic doses PMA expression. Two other...
Large-scale RNAi screening has become an important technology for identifying genes involved in biological processes of interest. However, the quality large-scale is often deteriorated by off-targets effects. In order to find statistically significant effector pathogen entry, we systematically analyzed entry pathways human host cells eight pathogens using image-based kinome-wide siRNA screens with siRNAs from three vendors. We propose a Parallel Mixed Model (PMM) approach that simultaneously...
Methods enabling the delivery of proteins into eukaryotic cells are essential to address protein functions. Here we propose broad applications cell biology for a tool based on bacterial type III secretion (T3S). We show that bacterial, viral, and human proteins, fused N-terminal fragment Yersinia enterocolitica T3S substrate YopE, effectively delivered target in fast controllable manner via injectisome extracellular bacteria. This method enables functional interaction studies by simultaneous...
IL-2 is known to play a critical role in regulating T lymphocyte proliferation. We show here that also provokes an instantaneous and sustained membrane ruffling cloned human or murine cells as well lectin-activated peripheral blood lymphocytes. In the IL-2-induced lamellipodia, tubulin depolymerized whereas actin strongly polymerized, forming caps. protein kinase C (PKC) independent, judged by absence of effects bisindolylmaleimide, efficient inhibitor all PKC isoforms. The formation...
After stimulation of the T cell receptor (TCR), tyrosine residues 292 and 315 in interdomain B protein kinase ZAP-70 become phosphorylated plausibly function as docking sites for Cbl Vav1, respectively. The two latter proteins have been suggested to serve substrates fine-tune its function. To address role these development primary cells, we generated mice that express molecules with Tyr Phe substitution at position (Y292F) or (Y315F). When analyzed a sensitized TCR transgenic background,...
The mouse pathogen Citrobacter rodentium is used to model infections with enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC EPEC). Pathogenesis commonly modelled in mice developing mild disease (e.g., C57BL/6). However, little known about host responses exhibiting severe colitis C3H/HeN), which arguably provide a more clinically relevant for human paediatric enteric infection. Infection of C3H/HeN C. results rapid colonic colonisation, coinciding induction key inflammatory...
Abstract The GTPase Rac controls signaling pathways often related to actin polymerization in various cell types. In T lymphocytes, is activated by Vav, a major component of the multiprotein transduction complex associated TCR. Although profound defects have been observed Vav-deficient mice, role corresponding early TCR has not tested directly. This question was investigated Jurkat cells transfected with either dominant-negative (RacN17) or constitutively active (RacV12) form Rac. expressing...
Background During pathogen infection, innate immunity is initiated via the recognition of microbial products by pattern receptors and subsequent activation transcription factors that upregulate proinflammatory genes. By controlling expression cytokines, chemokines, anti-bacterial peptides adhesion molecules, factor nuclear factor-kappa B (NF-κB) has a central function in this process. In typical model NF-κB activation, associated molecules triggers canonical pathway depends on...
Background Nuclear factor-κB (NF-κB) is a transcription factor that regulates the of genes involved in variety biological processes, including innate and adaptive immunity, stress responses cell proliferation. Constitutive or excessive NF-κB activity has been associated with inflammatory disorders higher risk cancer. In contrast to mechanisms controlling inducible activation, regulation basal activation not well understood. Here we test whether clathrin heavy chain (CHC) contributes...
Abstract Alpha-protein kinase 1 (ALPK1) is a pathogen recognition receptor that detects ADP-heptose (ADPH), lipopolysaccharide biosynthesis intermediate, recently described as pathogen-associated molecular pattern in Gram-negative bacteria. ADPH binding to ALPK1 activates its domain and triggers TIFA phosphorylation on threonine 9. This leads the assembly of large oligomers called TIFAsomes, activation NF-κB pro-inflammatory gene expression. Furthermore, mutations are associated with...