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Modulation by Card9 of the gut microbiota and its ability to produce Aryl hydrocarbon receptor agonists: mechanisms, therapeutic and biomarker potential in inflammatory bowel diseases – MARYLAND
The aims of the present project are to decipher the mechanisms involved in the modulation of the microbiota by Card9. For this purpose, we will take advantage of gnotobiotic animals, cre-lox technology, state-of-the-art transcriptomics, metabolomics and high-throughput sequencing, and of a very well
Understanding how IFN-gamma receptor nanoscale membrane dynamics control immune responses mediated by IFN-gamma – NanoGammaR
In this PRC project, we aim at determining how IFN-gR dynamically interacts with different nano-organizations/assemblies at the plasma membrane and how these interactions are regulated under physiological conditions to mount the efficient and controlled immune responses. In a recent breakthrough stu
Exon skipping and production of truncated immunoglobulin chains in plasma cells: towards antisense-mediated therapeutic perspectives – TIE-Skip
The “TIE-Skip” project (36 months, 2 teams) will address scientific issues pertinent to the B-cell-lineage and their implications in immunopathology, with specific focus on antibody-secreting plasma cells. The error-prone V(D)J recombination process generates out-of-frame V(D)J junctions in ~2/3 of
Understanding the function of Ikaros family proteins : from physiology to structure – IKAROS
The Ikaros family of transcription factors includes 4 related zinc finger DNA-binding proteins (Ikaros, Aiolos, Helios, Eos) that are expressed mainly in hematopoietic cells, where they are essential for immune cell differentiation and function. Studies in mouse and man have demonstrated the absolut
Role of the lung/gut/bone marrow axis and of the microbiota during influenza A virus infection – ACROBAT
Severe bacterial (pneumococcal) infections are commonly associated with influenza and are significant contributors to the excess morbidity and mortality of influenza. Today’s treatments of secondary bacterial infections are still not effective enough. Moreover, antibiotic resistance is a major issue
Innate lymphoid cells: functional analysis in zebrafish – ZF-ILC
Understanding how the different members of the immune system work together to protect us against disease, and how deregulated immune responses lead to pathology have a strong impact in public health. Innate lymphoid cells (ILCs) are the most recently discovered constituent of the immune system and t
Origin and function of intestinal epithelial tuft cells as effectors of type 2 immune responses – TUFTEFF
The intestinal epithelium represents the principal interface between our organism and the outside world (approximately 200 square meters). Whereas the main function of the intestinal epithelium consists in absorbing nutrients, this epithelium is also in direct contact with the highly variable compos
Stroma/Macrophage cross talk in the lymph node – StroMAC
Secondary lymphoid organs such as lymph nodes (LNs) are composed of leukocytes (~95%) and lymphoid stromal cells (~5%) that form the structural framework of these organs. Various specialized stromal cell subsets create dense three-dimensional (3D) cellular networks that control lymphocyte survival a
Deciphering the mechanisms of action of two antimalarial redox-active drugs with gametocytocidal and transmission-blocking properties - from yeast to malarial parasites – PlasmoPrim
With 429 000 deaths per year, malaria remains the most devastating parasitic disease for humans. It is caused by Plasmodium parasites and transmitted by Anopheles mosquitoes. The efficiency of artemisinin-based combination therapies (ACTs), the spearhead of malarial treatments, is now threatened by
Oxygen exposure in neutrophils activation and cell death: a double-edged sword – NEUTROXIA
Neutrophils are the most abundant circulating white blood cells. Due to their short lifespan in vitro (
Molecular regulation of monocyte differentiation: from mechanisms to therapeutic targets – MonoDiff
During inflammation, monocytes are rapidly recruited and differentiate in situ into monocyte-derived macrophages (mo-Mac) and monocyte-derived dendritic cells (mo-DC). During immune responses, mo-Mac are generally involved in clearance of pathogens, while mo-DC can stimulate T cells or transport ant
Modeling Differentiation and Exit in Germinal Centers through integrative single-cell analyses – MoDEx-GC
High affinity antibody responses to pathogens and vaccines require affinity maturation of antigen-specific B cells in germinal centers (GC). High affinity GC B cells are selected to exit the GC and differentiate to long-lived antibody-producing plasma cells and memory B cells, but the underlying mol
Probing Hematopoietic Stem Cell (HSC) directed immune response and memory – HSCmemory
Classically hematopoietic stem cells (HSC) have simply been seen as neutral suppliers of a sufficient number of mature cells, whereas the regulation of the immune response and long-term memory of previous challenges has been thought to be exclusively mediated by the differentiated cells of the immun
Heptose 1,7-bisphosphate sensing in gram-negative bacterial infections – HBPsensing
Bacterial infections constitute a major problem for human health. With the increase of antibiotic resistance, there is an urgent need for academic research to better characterize the virulence determinants associated to pathogens and envision new therapeutic strategies that are based on a deep under
Membrane remodeling by enveloped viruses of Archaea – ENVIRA
Membrane remodeling is a fundamental and necessary process underlying proper functioning of cellular organisms in all three domains of life. Much of our knowledge on the mechanisms of membrane fusion and scission, two of the key steps during remodeling of biological membranes, comes from studies on
THE HOST FACTORS OF ZIKA VIRUS NEURO-PATHOGENESIS – ZIKAHOST
Zika virus (ZIKV) is a mosquito-borne Flavivirus that causes Zika disease characterized by fever, rash, arthralgia and conjunctivitis which, given the rapid worldwide spread of the virus, is now considered an emerging infectious disease. Of particular concern are recent reports of neurological compl
Do sugars dictate the pathogenicity of antibodies – Sugars-in-MS
Antibodies (Abs) exert their function by binding to distinct Fc receptors and complement. The affinity of these interactions is traditionally ascribed to the Ab isotype. At least for the IgGs this view is evolving. N-linked glycans are increasingly proposed to influence binding to the classical Fc-g
Impact of CD95L, in IL17-expressing T-cell dysfunction in human systemic lupus erythematosus. – FASILE
Chronic inflammatory diseases (IDs) are the third cause of death in developed countries, after cancer and cardiovascular disorders, and their prevalence is growing in westernized countries. These diseases constitute a heterogeneous group of illnesses, including non-exhaustively, rheumatic diseases (
Exploring how meningitis-associated hyper-virulent CC17 group B Streptococcus infects the brain – strepB2brain
Meningitis may be caused by infection with microorganisms such as bacteria, viruses, fungi or parasites. Bacterial meningitis is the most common serious infection of the central nervous system and a major cause of death and disability worldwide, especially in children. Group B Streptococcus (GBS), a
Understanding the mechanism of Yellow Fever 17D vaccine efficacy: An immuno-structural approach towards the design of a Pan-flavivirus vaccine – FLAVIMMUNITY
Yellow fever virus re-emergence in Africa in a globalized economy presents a significant risk of spillover to unaffected areas in Asia. Despite the availability of the YF17D vaccine, its low supply and our poor insight into viral biology and vaccine immunogenicity bear the risk to be unprepared for
Checkpoint mechanisms in the innate immune sensor STING – STINGCHECK
Sensing foreign DNA is a universal mechanism of immunity. In animals, the cGAS-STING pathway of DNA sensing plays critical roles in viral & bacterial infections, in auto-immunity and in vaccines. This universality implies that cGAS-STING is tightly regulated. In response to DNA, cGAS synthesizes a s
Role of phosphoinositides in infections by the Q fever pathogen Coxiella burnetii – QPiD
A fundamental step for the survival and replication of intravacuolar bacterial pathogens is the establishment of a replicative niche inside host cells. This is achieved by secreting bacterial effector proteins in the cytoplasm of the infected cells by specialised secretion systems. Bacterial effecto
A Serine/threonine kinase promotes resistance to antimicrobial coumpounds crucial during colonization in Clostridium difficile – DifKin
Clostridium difficile (CD) is the leading cause of intestinal nosocomial post-antibiotic infections. The impact of CD infection (CDI) in hospitals is considerable in terms of mortality, morbidity and disease management as well as for its financial burden. Due to the unsatisfactory nature of standard
Systems analysis of antigen-presenting cells in human sepsis – DENDRISEPSIS
Sepsis is a common life-threatening inflammatory response to infection and is the leading cause of death in the intensive care unit. Septic patients exhibit a complex immunosuppressive response affecting both innate and adaptive components of immunity, with a possible link to nosocomial infections.
Cellular metabolism of Treg in the control of chronic inflammatory diseases – MetaTreg
Cellular metabolism is becoming an emerging field of investigation in immunology. For instance, it has been recently shown that a switch from oxidative phosphorylation to aerobic glycolysis in conventional T cells is a prerequisite for their proper activation. CD4+Foxp3+ regulatory T cells (Tregs) p
Visualizing interactions between XCR1+ dendritic cells and lymphocytes and deciphering their molecular regulation – XCR1DirectingCells
XCR1+ dendritic cells (DC) represent a minor population of immune cells in human and mouse. Yet they are strong activators of innate lymphoid cells (ILC) and CD8+ T cells, which effector responses allow efficient control of certain infections and cancer. With this project, we will explore a novel fu
STING-mediated antiviral immunity in Drosophila – Roxanne
The goal of this application is to use the model organism Drosophila melanogaster to shed light on the ancestral function of the cGAS/STING innate immunity pathway. Activation of this pathway in mammals plays a critical role in the induction of interferons, with beneficial (immunotherapy, vaccine ad
Structure and dynamics of signaling networks controlling functional outcomes in primary T lymphocytes – LYMPHOSCAN
T cells are major effectors of the immune response. They expressed the surface T cell receptor (TCR) that recognize specific antigenic peptides in the context of major histocompatibility complex (pMHC) molecules. Affinities of these interactions and the number of engaged TCRs determine the nature an
Dynamics of Dendritic Cell populations during inflammation – DynaDCs
Conventional dendritic cells (cDCs) are necessary to induce adaptive immunity. Tissue resident cDCs migrate from inflamed tissues to lymphoid organs where they initiate immune response. A consequence of this process is the rapid depletion of tissue resident cDCs during immune responses. Therefore, t
Chemokine recognition and downstream signaling in atypical and viral receptors – CHEMSPEC
Chemokines receptors (CKRs) form a subfamily of G-protein coupled receptors that play critical roles in immune modulation, wound healing, inflammation and host-pathogen interactions. A particularly interesting subclass of CKRs are atypical and viral CKRs, a number of which have evolved unique proper
Identification of the inflammasome involved in Anti-Virulence Immunity: Impact on how we fight against bacteremia – AVI
How the innate immune system recognizes virulent microbes? Knowing that pathogenic bacteria express specifically virulence factors, we have worked-out to identify defense mechanisms that respond to microbial virulence factors. We have unraveled the host monitoring of the activity of virulence factor
Molecular signaling during red blood cell invasion by malaria parasites – MolSigMal
Malaria continues to be a major public health problem in the tropical world with around 214 million cases in 2015 that resulted in 438,000 deaths. Malaria is caused by several Plasmodium species of which P. falciparum is the most lethal. The rise and spread of artemisinin-resistant P. falciparum str