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The aim of our project is to better understand the mechanisms of suppression of Foxp3 regulatory T cells (Tregs) in certain inflammatory diseases such as multiple sclerosis, colitis or cancers. For this, we will use genetically modified mice in which the expression of the TNFR2 and 4-1BB co-stimulat

The chemokine receptor CXCR4 is a protein of great interest in basic science and medical research., because it is expressed by many cell types and has multiple biological roles, including cell migration and signaling. Expression levels of CXCR4 are increased in lupus and arthritis and correlate with

Plague is a deadly zoonosis caused by the bacterium Yersinia pestis and transmitted by fleas. This re-emerging disease is a global public health threat. The emergence of strains that are multi-resistant to the antibiotics used against the disease and the absence of a vaccine force us to think about

Many viral, bacterial and eukaryotic pathogens have co-evolved strategies to modulate the expression profile of their mammalian host cells promoting their own survival. Underlying regulatory mechanisms are only poorly understood, despite their relevance in human disease and host-directed therapy. EL

TREATABLE project focuses on tuberculosis that remains a major global-health threat, also causing a quarter of the global antimicrobial resistance emergency, and is further exacerbated by the COVID-19 pandemic. The ability of Mycobacterium tuberculosis to persist despite the pressure exerted by the

Accumulating evidences revealed that disturbances of the host-microbiota relationship can results in microbiota encroachment which associates with the promotion of chronic intestinal inflammation. For example, we observed that consumption of dietary emulsifiers leads to alterations in microbiota tha

Plasmacytoid dendritic cells (pDC) produce huge amounts of type I and III interferons (IFN) during most systemic viral infections. As the response to IFN activates both cell-intrinsic antiviral defense and innate and adaptive immunity, pDC are considered to exert key immunoactivating functions in an

The phylum Apicomplexa comprises parasites of human and veterinary importance, among which Plasmodium falciparum, the deadliest Plasmodium species responsible for human malaria. This parasite displays a complex life cycle alternating between its mosquito vector and the human host. The symptomatic ph

Many arboviruses cause neurological damage, including viruses of the genus Flavivirus, such as Zika virus and in some cases Dengue virus. Clinical symptomatology, blood and brain biomarkers, as well as mechanisms underlying their neurovirulence and associated neuronal pathologies, are only partially

Pyrin, encoded by MEFV, detects the inhibition of RhoA GTPases by bacterial toxins and mounts an inflammasome complex. Pyrin deregulation plays a key role in two autoinflammatory diseases. We have demonstrated that pyrin dephosphorylation alone is not sufficient to induce inflammasome activation, in

Neutrophils are the most abundant leukocytes and represent the first line of defence against pathogenic bacteria. Their antimicrobial activity relies on their ability to trigger a myeloperoxidase (MPO)-dependent oxidative burst. Concomitant to the well-documented production of hypochlorous acid (HOC

Infectious diseases are a major threat to human health and predictions suggest that over the next few decades, these will account for one of five deaths globally. In times where emergence of antibiotic-resistance in bacteria is occurring worldwide, understanding how bacteria cause disease is essenti

T cells are essential for immune responses, but they become dysfunctional and less proliferative during aging. Aging is characterized by increased aneuploidy. The hallmark is the exponential loss of Y chromosome (LOY) in leukocytes during male aging, which is associated with increased disease risk a

The NF-kB family of transcription factors plays essential roles in multiple physiological and pathological processes. NF-kB activation consists in a rapid and tight coordination of gene transcription between hundred target genes, the majority being involved in cell differentiation, cell proliferatio

Hepatitis D is the most severe form of chonic viral hepatitis. Hepatitis D virus (HDV) is a small satellite virus of hepatitis B virus and to date, no treatment allows viral clearance in chonically infected patients. A dual screening approach identified 191 new host factors for HDV infection, includ

T cells are central in adaptive immunity. On antigen encounter, the T-cell antigen receptor (TCR) becomes engaged and in concert with context-sensitive co-stimulators, such as CD28, induces T-cell activation, differentiation and function. CD28 signaling was recently shown to relies on the CARMIL2 mo

The role of Eomes in the CD4+ T cells remains mostly unclear and differs regarding the disease, context and Th subsets. However, what seems consistent is the importance of Eomes in inflammation as suggested by genetic association studies. Our recent results revealed that Eomes controls chronic neuro

While research efforts focused on CD8+ T activation in lymph node and trafficking to tumors, little is known on CD8+ Tissue-Resident Memory (TRM) cell function at the tumor site. In this proposal, we will measure CD8+TRM cytotoxic capacities at the single cell level, in human non-small cell lung can

The interferon response protects cells from invading viruses by inducing the expression of around 2,000 interferon-stimulated genes (ISGs). Only a handful of these ISGs have been well characterized. Using a loss-of-function strategy, we screened an original library of 1156 siRNAs targeting around 38

The respiratory syncytial virus (RSV) is a major and ubiquitous agent of respiratory viral infections in humans. It is responsible for more than 33 million cases/year of bronchiolitis in children worldwide and is also associated with a substantial disease burden in adults comparable to influenza, wi

Variability in response to Ebola virus (EBOV) exposure and infection is now well-established. In particular, it was found that exposure to EBOV could result in asymptomatic or pauci-symptomatic infections, and that some highly exposed individuals could be considered as non-infected. Based on these o

The thymus provides the environment for the development and selection of T cells. Thymic epithelial cells coordinate virtually all stages of T cell development, providing key cytokines, chemokines and ligands for the commitment, survival and proliferation of thymocytes and also for positive and nega

NeuroMuscular Blocking Agents (NMBA; curares) relax skeletal muscles to facilitate surgeries and permit intubation, but lead to adverse reactions: (a) severe hypersensitivity reactions (anaphylaxis) thought to rely on pre-existing anti-NMBA antibodies; (b) complications due to postoperative residual

Borna disease virus (BoDV), a single-stranded RNA virus of negative polarity, has puzzled researchers for decades, because of its neurotropism and non-cytolytic multiplication strategy. Its recent recognition as a zoonotic agent causing severe encephalitis and brain dysfunction has provided further

Malaria remains a major cause of death and morbidity worldwide and no efficacious vaccine is available. The liver stage (LS), an obligatory and asymptomatic phase of parasite’s life cycle, is an ideal vaccine target but our knowledge of human immunity to LS is scarce. Very few antigens (Ags) are kno

Bacterial effector proteins manipulating host cell functions play a key role in virulence. Our consortium identified sub-nuclear associated proteins (SNAPs) translocated by the stealth bacterial pathogens Brucella abortus and Coxiella burnetii, that localize at promyelocytic leukemia nuclear bodies

Persistent viral infections of the male genital tract have far-reaching implication for human health, including diseases spreading. The emerging arbovirus Zika (ZIKV)is sexually transmitted by cured men and we demonstrated it persistently infects the human testis. We postulate that persistent testis

Epidemics caused by viruses transmitted by mosquitoes to humans, such as dengue fever, are an increasing burden for global health. In the absence of drugs and efficient vaccines, innovative strategies based on the release of lab-engineered mosquitoes that are unable to transmit diseases have gained

In this proposal, we will determine the role of the mucosal cytokine Interferon lambda IFN-? in controlling the capacity of intestinal epithelial cells to orchestrate tissue regeneration in IBD and the microbial determinants and cellular sources responsible for IFN-? expression in the gut in health

Dendritic cells (DC) are crucial players in the initiation of adaptive immune response. A key feature of DC is their high capacity to capture antigens in peripheral tissues and migrate to draining lymph nodes (LN). In psoriasis, migratory IL-23-secreting DC drive T cell activation in LN and IL-17 r

Urinary tract infections (UTI) are primarily caused by uropathogenic strains of E. coli (UPEC) that are genetically related to extra-intestinal pathogenic E. coli (ExPEC). UTI are common infections, impacting > 150 million individuals annually, with a strong sex bias towards female incidence, and a

Acute Myeloid Leukemias (AML) are a heterogeneous group of blood cancers. Recently, the presence of neoantigens tumor-specific T cells has been reported, opening a new area of research in AML. Our project will explore whether these T cells response can be broadly identified in AML using advances met

Hidradenitis Suppurativa (HS), also known as Verneuil’s disease, is an incurable skin disease manifesting as recurrent, painful abscesses leading to significant scarring. The estimated worldwide prevalence of HS is around 1%, with highest rates in Europe (1-4%) and a more than 2-fold higher incidenc

Feeding is an essential function of living organisms, but comes with the risk of ingesting pathogens and toxins. As a consequence, the intestine is home to a large immune system, as well as to the largest network of peripheral neurons regulating peristalsis, and monitoring food, noxious substances a

The related Apicomplexa parasites Toxoplasma gondii and Plasmodium falciparum are the causative agents of the human diseases toxoplasmosis and malaria, respectively. These diseases still have a major global health impact due to the parasite’s ability to survive in and cycle through different host en

The genome is divided into several compartments: the nucleosome, supranucleosome and nucleus. Gene position is precise and dynamic in the nucleus; genes can interact with each other via their enhancer and promoter regions. The immunoglobulin heavy chain locus harbors two enhancers: 3'RR and Eµ-MAR.

B cells have a remarkable capacity to alter their immunoglobulin (Ig) loci. Activated mature B cells diversify Ig genes through somatic hypermutation (SHM) and class switch recombination (CSR). SHM yields higher antibody affinity carried by positively selected cells. In parallel, negative selection

Expansion and proliferation of antigen-specific T and B cells is a prerequisite for an effective immune response. We recently described a new combined immunodeficiency caused by mutations in CTPS1, a gene coding for CTP Synthetase 1 (CTPS1), an enzyme involved in the de novo synthesis of the CTP nuc

The intestinal epithelium, constituted of a single cell layer, represents the only border with the hostile environment in the gut lumen, containing foreign organisms and other toxic compounds. Maintenance of homeostasis requires crosstalk between the epithelium and the immune system, both at the ste

STress response and Immunity Modulation (STIM) is an exploratory research project at the interface of cell biology, genomics and immunology, aiming at unraveling how the Integrated Stress Response (ISR), contributes to the regulation of immunity and potentially to auto-immunity onset. The ISR is es

Along evolution, intracellular bacterial pathogens have developed elaborated means to counter the immune response of their host in order to establish optimal replicative niches in which they replicate in high numbers. This is achieved by the secretion of bacterial effector proteins that divert the f

Secretion system (SS)-mediated delivery of effector proteins into host cells plays a key role in bacterial virulence. Despite recent progress in the structure-function studies of various SS (e.g. T3SS, T4SS, T6SS, etc.), the signals that activate effector transfer have largely remained a closed book

Plasmodium vivax causes significant morbidity in the tropical world. A vaccine that protects against P. vivax and reduces transmission would help efforts to eliminate malaria. The P. vivax Duffy binding protein (PvDBP), a leading vaccine candidate, binds the Duffy antigen receptor (DARC) to mediate

Pneumonia was the leading cause of communicable diseases and the second cause of disability-adjusted life-years in the world in 2019, even before the COVID-19 pandemic. Pneumonia can be either acquired in the community (community-acquired pneumonia, CAP) or during hospitalization (Hospital-acquired

Prions are lethal proteinaceous pathogens with major public-health risks due to their zoonotic and iatrogenic potential. They are composed of aggregated, misfolded conformers of the host-encoded prion protein that progressively deposit in the brain by a self-perpetuating reaction. The underlying mol

Mutually exclusive expression of the var gene family is critical for infection and immune evasion by the deadliest human malaria parasite, Plasmodium falciparum. All but one var gene are silenced in heterochromatic clusters at the nuclear periphery, and activation is associated with spatial separati

Macrophages play key roles in tissue regeneration and inflammation at steady-state, two processes that are essential to maintain tissue homeostasis and, if dis-regulated, can lead to pathology. We have recently discovered a peculiar population of macrophages in the distal colon that is needed to loc

The Hu-Thy-L project aims to unravel how genetic variation impacts on chromatin accessibility, epigenetic modifications and/or transcription factors binding, leading to differences in thymocyte differentiation. The understanding of a “fine tuning” of thymopoiesis may improve our basic knowledge of h

Hematopoietic stem cells (HSC) are long-lived cells that allow the regeneration of all blood cells. More and more data allow us to consider HSC as an immune cell. Indeed, they are able to recognize directly certain pathogens or inflammatory cytokines produced at the site of infection. They will resp