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Non-glycolytic pathways in glycosomes: novel functions for trypanosome development and virulence – GLYCONOV
Trypanosomes have a very atypical intermediate metabolism, including specific metabolic pathways located in the glycosomes, peroxisome-like organelles containing mainly glycolytic enzymes. GLYCONOV is an original project on unexplored or poorly explored non-glycolytic glycosomal metabolic pathways f
Crosstalk of Glucocorticoid Receptor and AMP-activated protein Kinase in macrophages during inflammation and tissue repair – GR-AMPK
Inflammation after infectious or sterile traumatic insult and its subsequent resolution is a balanced process to combat pathogens and to induce tissue repair while avoiding aberrant inflammation-induced organ damage. Macrophages are central players by participating in both inflammatory and repair pr
The human body facing and defending from chemical skin allergens reacting by alternative mechanisms: understanding from the molecule to the tissue – DEFCHEMSKALL
Exposure to allergens and the risk of skin sensitization are an essential regulatory issue within industry. It is thus crucial to predict the sensitization potential of chemicals before their use in consumer products. To perform risk assessment, studies helping to understand all mechanisms leading t
Mechanical and chemical guiding of immune cells : from quantitative biophysical assays to the study of infection – recrute
1- Elaboration of model microenvironments 2- Quantitative study of mechanisms underlying arrest, migration and guiding of leucocytes on patterned substrates 3-Comparative in vitro and in vivo study of biochemical signals orchestrating lymph node traffic 4-Study of recruitment properties of leucoc
Control of dendritic cell migration and immune function by physical constraints and matrix components that control dendritic cell migration and immune function – PhyMAX
Dendritic cells (DCs) constitute a complex cell population whose main function is to link the innate and adaptive immune responses, thereby playing a critical role in both the establishment of tolerance and immunity. In peripheral tissues, immature DCs continuously sample their environment thanks to
Characterization of PI3K/AKT/mTOR –pathway in human lymphocytes – PIKimun
The overall objective of this proposal is to better understand the physiopathogeny of PADs associated with hyper-activation of PI3K/AKT/mTOR signalling, to analyze the impact of “hyper-activated” PI3K signalling on gene expression, lymphocyte function and differentiation and to identify novel molecu
Role of CX3CR1 expression on Monocytes during sepsis – a translational study – CMOS
Sepsis is defined as a widespread inflammation secondary to an infection. It will strike more people every year than lung, breast and prostate cancers combined and its incidence is raising. Sepsis is a dual disease, inflammation is predominant in the early phase and leads to organ failures, while in
Alternative roles for autophagy receptors in host-pathogen interactions – AutoHostPath
Understanding the molecular basis of host-pathogen interactions is critical for the discovery of new therapeutic approaches to treat infectious diseases, which in the face of increasing antibiotic resistance and emerging pathogens, is a major priority medical research in Europe. Studying the signall
The roles of NKp46 in Innate Lymphoid cells – NKp46+-ILCs
Specific aim#1: What is/are the ligand(s) of NKp46? The first part of this program was built on the results of team 1 (EV) showing that a seric complex containing the Complement Factor P (CFP) is involved in NKp46 recognition. The objectives was to (i) characterize the contribution of CFP for NKp46
Role of the microbiome in the macrophage response to Mycobacterium tuberculosis: A research program to integrate microbiota, metabolism and immunity – MMI-TB
BACKGROUND. Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB) in humans, still claims around 1.5 million lives yearly. In fact, TB is among the three most deadly diseases due to a single infectious agent, justifying the need to better understand host-Mtb interactions. In p
Molecular and cellular caracterization of novel bacterial nucleomodulins – NucPath
(1) Identify their eukaryotic targets. This is an essential step to understand the mode of action of each nucleomodulin and which cellular pathways are being targeted during infection. (2) Undertake structure-function studies to identify key functional domains involved in the nuclear-modulatory pr
Implication of prokaryotic Rab-GTPases in pathogenesis and disease – ProRab
Pathogens that are able to enter and multiply within human cells are responsible for a large disease burden worldwide. Legionella pneumophila and Legionella longbeachae the causative agents of a severe pneumonia called Legionnaires’ disease are belonging to these intracellular bacterial pathogens. T
Self-mediated shaping of naïve CD4 T cell effector fate – Self-shaped-CD4_TN
Altogether, our recent results suggest that continuous / chronic interactions with self-MHC shape both the phenotype of CD4 TN cells and their behavior in the effector phase by favoring their differentiation into iTreg cells. We now plan to extend this study by: 1- Identifying the tonic TCR signali
Human infection with zoonotic simian foamy retroviruses: role of virological and immunological factors in restricting viral emergence – REEMFOAMY
The public health relevance of retroviruses of zoonotic origin is illustrated by the human immunodeficiency virus (HIV) epidemic, the worldwide distribution of human T-lymphotropic viruses (HTLVs), and the morbidity and mortality associated with both sets of viruses. Both HIVs and HTLVs emerged in t
Interactions of Listeria monocytogenes with the intestinal epithelium – OrganoList
The intestinal epithelium constitutes a tight barrier for enteric microorganisms, which only few enteroinvasive pathogens, including Listeria monocytogenes (Lm) have the ability to cross. We have shown that Lm accesses the intestinal lamina propria via goblet cells by transcytosis. However, the prec
Single Cell Analysis of Plasmacytoid dendritic cells to understand their heterogeneity for INterferon production – SCAPIN
Our ability to defend ourselves against infections and cancer relies on the coordination of our immune responses, largely orchestrated by cytokines in particular type I and III interferons (IFN). A striking example of the biological process under study is the production of enormous amounts of IFN by
Cytoskeleton remodeling by storage endosomes – molecular mechanisms and impact on the immune response – CytoEndoStor
The main goal of CytoEndoStor project is to uncover the molecular mechanism by which SRSE affects cytoskeleton dynamics and estimate their impact in vivo on T cell and DC function. To this end, we propose to: 1. Identify the molecular interactions that control SRSE trafficking; 2. Characterize SRSE
Innate lymphoid cells and immunological memory – ILC3_MEMORY
Within the lymphoid compartment, B and T cells that deliver adaptive immunity are well recognized as essential players in the clearance of pathogens and development of immunological memory. In contrast, myeloid cells and other innate lymphocytes are critical players in the early stages of an immune
Chemical stimulation of the innate immune response with ChX710: Toward a new class of antiviral molecules – ChemInnate
Most cells express a set of membrane and cytoplasmic receptors to detect viral RNA and DNA molecules: Pattern Recognition Receptors (PRRs). These receptors control the innate immune response and activate the synthesis of interferons during a viral infection. The aim of the ChemInnate project is to i
Mechanisms of colonization and dissemination of a bacterial pathogen in a human population, the example of Neisseria meningitidis – PATHONEM
Much has been done in the understanding of the mechanisms allowing bacteria to disseminate from their port-of-entry. On the other hand, the understanding of how bacterial pathogens colonize their niche at the port-of-entry remains poorly understood, the study of this important step has been hampered
Mechanisms of complement-induced inflammation and endothelial cell damage in hemolytic conditions – INFLACOMP
We will study the role of heme and other hemolysis derived products in the stimulation of endothelial cells and inflammatory leucocytes and in their ability to activate complement. We aim to understand the cellular, molecular and genetic mechanisms of heme-induced complement activation on endothelia
Role of TNFR2 expressed by Treg in autoimmune diseases and therapeutic implications – TETRAD
The immune system, which is part of the white blood cells, can effectively fight against infectious diseases. In more than 5% of the population, this system dysfunctions, destroys certain cells of the body, triggering an autoimmune disease. Different types of autoimmune diseases are described depend
Dissection of the molecular genetics of natural killer cell deficiencies in humans – NKD
To better understand the role of NK cells in humans, we intend to recruit individuals with a NK cells deficiency. The clinical follow-up of these individuals will determine if they have a predisposition to develop some infectious diseases, and which ones, some cancers or other diseases. The identifi
Regulation of the lymphoid system and immunopathology by ILC3s – LymphoILC3
The objectives of this project are to determine the role of: 1. ILC3s in the development and function of lymphoid tissues - where adaptive immune responses are initiated 2. ILC3s in the regulation of adaptive immune responses and immunopathology - during primary and memory responses in defe
Novel common host targets during bacterial invasion of humans – StopBugEntry
Infectious diseases are a major public health problem, and identification of novel potential therapeutic candidates is mandatory in a context of growing antibiotic resistance. As classical infection biology approaches are nearly exhausted in their current capacity to address the emergence of multi-d