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Circadian clocks sustain rhythmic patterns in behavior and physiology and increase the flexibility of the organisms to adapt to cyclic changes in the environment. Disrupted circadian rhythmicity, a well-known aspect of modern-day society, promotes the pathophysiology of a wide variety of diseases. C

During co-evolution with their hosts, bacterial pathogens have evolved an impressive variety of strategies to take control of cellular pathways and avoid host defence mechanisms in order to establish a productive infection. Among the range of tools dedicated to host manipulation, pathogenic intracel

B-cell depletion is a highly promising therapy to treat patients with autoimmune diseases such as multiple sclerosis. However, such therapy is not risk free and could induced side-effects such as severe systemic infection. Cytokine production by B cells have a major impact on the development of neur

Regulatory T cells (Treg) are of paramount importance for establishing self-tolerance and their manipulation harbors enormous therapeutic potential in a wide spectrum of diseases, ranging from autoimmunity to chronic inflammatory and infectious disorders. Our recent studies revealed that Themis1 and

Obesity is a global health problem affecting 13% of the world population. There are multiple complications associated with obesity, including metabolic syndrome, type II diabetes, non-alcoholic fatty liver disease, atherosclerosis and ischemic cardiovascular disease. These complications account for

The inopportune stimulation of immune checkpoints (IC) can lead to a temporary silencing of the immune system, which can be deleterious in pathological situations such as infections or cancers. The biological mechanisms controlling the activity of these receptors are still unclear to this day. We ha

Streptococcus pneumoniae(PN) is a human nasopharyngeal commensal and major aetiological agent of bacterial meningitis. Our preliminary results indicate that cytotoxicity linked to PN and its major virulence factor pneumolysin (Ply) implicates calcium (Ca2+) signalling mediated by connexins (Cxs), th

Bacterial infectious diseases are a major concern for human health. The use of antibiotics to treat them has been a major success in medicine. However, its efficacy has gradually decreased due to the rapid emergence of multi-drug-resistance mechanisms. The identification of new microbial targets is

Clostridium difficile is the leading cause of intestinal nosocomial post-antibiotic infections. The impact of C. difficile infection (CDI) in hospitals is considerable in terms of mortality, morbidity and disease management as well as for its social economic burden. Importantly, relapse of CDI, whic

By studying bacterial and eukaryotic EVs the BioEV proposal aims to identify their role(s) in host-pathogen interaction and disease by deciphering the molecular mechanisms of the secretion and delivery of bacterial EVs in human cells during infection and the impact of Lp infection on hEVs. Furthermo

Specifically, we will characterize the evolutionary and functional diversification of a major antiviral effector in bats, the protein kinase R (PKR), in which we found rapid and unique functional adaptations at the molecular and genomic level. Here, we have characterized the functional diversificati

Viruses evolved strategies to disseminate by hiding into immune cells and enhance their migrating properties. Viruses induce drastic subcellular rearrangements that may lead to particular types of migratory behavior, but the underlying mechanisms remain poorly understood. We aim at unravelling the m

Tissue-resident macrophages (TMs), including epidermal Langerhans cells (LCs), are long-lived cells able to proliferate. Their ontogeny and adaptation to different organs have been studied in great details, yet their physiological maintenance deserves further investigations. Autophagy, a catabolic p

Sepsis causes more than 5 million deaths worldwide with an estimated cost of $ 17 billion annually in the USA. It is now assumed that most of the death is due to sepsis-induced immune suppression (SIIS) for which there is no FDA-approved specific therapeutic option. This SIIS renders septic patients

The goal of this project is to obtain a comprehensive overview of microbiota influence on the mucosal immune system through its interaction with Peyer’s patch (PP) phagocytes. We aim to: 1) define the different steps of the intestinal immunity maturation in PP at weaning time, when reshaping of t

Germinal centres (GC) are dynamic microenvironments in which, during T cell-dependent responses, mature B cells differentiate into memory B and antibody (Ab)-secreting plasma cells (PC). After antigen (Ag) encounter and interaction with Ag-specific follicular helper T cells (Tfh), B cells undergo 1)

New therapeutic strategies are required to reduce the incidence of human tuberculosis worldwide. This requires a better understanding of the key factors of the infectious agent contributing to pathogenesis and transmission. Tuberculosis-causing bacilli (TB bacilli) have evolved unique abilities to s

Evolution has provided effective ways of protecting man from external dangers while prospering from opportunities. The gut microbiota is a complex mixture of microbes that are continuously challenging the integrity of the intestinal barrier while at the same time providing numerous metabolic advanta

The main focus of the project is the AMP-activated protein kinase (AMPK), the master regulator of global cellular metabolism. Because of emerging single-cell scale technologies revealing a significant spatial heterogeneity in hepatic AMPK gene expression and function, and because Plasmodium hepatic

Intracellular pathogens adopt two distinct strategies to survive in their host cells: either hijacking the cellular endomembrane system and replicating inside membrane-enclosed vacuoles, or accessing the cytosol. The foodborne, facultative intracellular pathogen Listeria monocytogenes has been descr

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for crippling disease in humans. At present, there is no commercially available antiviral agents or vaccines to treat CHIKV infection. We have just identified the FHL1 protein as a major host factor for CHIKV replication. FHL1 is h

In this project, we will assess how the differentiation program generated in the thymus is modified by tissue and environmental cues to determine the positioning and effector functions of MAITs in the skin at steady state and during wound healing. This will provide the grounds to determine the way M

ILC2 are major players in the initiation of allergic asthma. We have shown for the first time in previous studies that there is a sex bias in this population. Tissues from females have increased numbers of ILC2 in both homeostatic and inflammatory conditions. We assessed the role of sex hormones in

Asthma is the most common chronic lung disease affecting 300 million people worldwide. Obesity is an important risk factor for asthma, but the underlying mechanisms through which obesity potentiates asthma remain poorly understood. The anti-IgE therapeutic antibody omalizumab is efficient in many pa

Our overall goal was to determine the mechanism of action of ISG20, an RNase that according to our previous studies, can discriminate endogenous RNAs on which it has no effects, from exogenous RNAs (viral) from which ISG20 blocks translation. The proposed approaches involved a thorough characteriza

There has been considerable effort the past few years to study the human microbiota and its link to human health. These studies revealed numerous important univariate features associated with changes in the microbiomes. They also called into question the current strategy focusing on associations wit

Influenza A virus (IAV) enters the cells via endocytosis and a pH decrease is required for viral and endosomal membranes fusion, and subsequent access of the viral ribonucleoprotein complexes to the cytosol. Endosomal acidification is key to antigen degradation and presentation to immune cells. We h

T lymphocytes perceive and respond to their environment by engaging receptors and transmitting intracellular messages through signal transduction cascades. This process is controlled by networks of proteins that bind to each other, dissociate, forming multiple signalosomes, which advance signal prog

To fulfill their functions, immune cells continuously integrate chemical and physical signals from their environment. While many studies have highlighted the role of chemical mediators in immune responses, the physical changes in tissues have been less explored. The main objectives of this project w

There is a sex bias in humoral immunity in humans and mice. In adults of childbearing age, basal immunoglobulin concentration, B cell count and antibody responses are higher in females compared to males. This difference is also observed in the immune response against RNA viruses (influenza viruses).

1. Define the cis-regulatory elements important for IKZF1 gene expression in BCP-ALL. 2. Determine and characterize the trans-regulatory regulating IKZF1 gene expression in BCP-ALL. 3. Identify if these elements are target for alteration in BCP-ALL causing low IKZF1 expression. We have identified se

Mosquito-borne flaviviruses, such as dengue, Zika, West Nile virus, and yellow fever, are a growing concern globally. The number of cases continues to increase, especially in tropical and subtropical regions, due to factors such as climate change and urbanization. Because of these same factors, the

C. difficile poses a serious, ongoing, public health threat. Patients are typically colonized by C. difficile after antibiotics treatment, which disrupts the intestinal microbiota homeostasis. ß-lactam antibiotics are recognized as major causative agents of C. difficile infection but the molecular m