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Priming T cell responses in old age – PriCelAge
Cellular immunity, mediated by T lymphocytes, is very important for the host response to various pathogens and cancers. The naive T cell compartment is essential because it is the basis for the induction of T cell responses. Our hypothesis is that quantitative and qualitative alterations of naive T
Role of the TIM and TAM receptors during dengue virus infection – TIMTAMDEN
Dengue disease, caused by four dengue virus (DV) serotypes, has emerged as the most important mosquito-borne viral disease of humans and is now a major global health concern. The molecular bases of DV-host cell interactions leading to virus entry are poorly understood, hampering the discovery of new
Thioamide Activation for the Tuberculosis World – Tea-4-Two
The main objective is to understand how this new generation of drug molecules reprogram the bio-activation pathway of ethionamide, to develop compounds with optimal pharmacological properties, to study whether these compounds can be successfully used against multidrug resistant and extremely drug re
Lupus multiplex families in the identification of new gene defects with strong phenotypic effects: from gene discovery to gene function – Lumugene
Systemic Lupus erythematous (SLE) is generally considered as a multifactorial disease, and genome wide association studies (GWAS) have identified more than 30 convincing disease-associated loci. Although these GWAS have greatly added to our understanding of lupus pathogenesis, the identified genetic
INTESTINAL TUFT CELLS: NEW PLAYERS IN INTESTINAL IMMUNE REGULATION – IMMUNOTUFT
Our preliminary data suggest a role for tuft cells in the host defence following infections with enteric parasites. We will combine in vivo and in vitro approches to analyse the contribution of intestinal tuft cells in type 2 immune responses against the helminth Nippostrongylus brasiliensis. We hav
A new model of innate immune response regulation by the nucleotide metabolism – INNATENUCLEOTIDES
We found that in human cells presenting a specific defect in DNA repair and nucleotide metabolism, an innate immune response is constitutively activated. Our project aims (1) to characterize the ealy events leading to the innate immune response in cells presenting a nucleotide pool defect, (2) to ev
Outsmarting Beta-lactam resistance in Meningococci and Pneumococci – ORBiMP
Improving beta-lactams efficiency will address the escalating resistance problem of major bacterial pathogens expressing Penicillin-Binding Proteins (PBPs) with low affinity for the antibiotics. These variant PBPs are fully active in incorporating the peptidoglycan precursor in the cell wall despite
Deciphering parasite-specific factors involved in retrograde trafficking and virulence of Toxoplasma gondii – APISORTING
The phylum Apicomplexa comprises a large group of obligate intracellular parasites of wide human and agricultural significance. Most notable is Plasmodium spp., the causative agents of malaria, and Toxoplasma gondii, responsible for diseases of the developing fetus and immune compromised individuals
Large-scale genomic re-encoding of RNA viruses for producing live-attenuated vaccine candidates – RNA Vacci-Code
Protecting humans against emerging RNA viral pathogens is a crucial challenge. Vaccines –specifically live attenuated vaccines- are the most efficient way to provide rapidly lasting protection to large populations. However, producing rapidly new attenuated vaccines remains difficult and quite unpre
Autophagy in antiviral immunity – AutoVirim
Autophagy is a catabolic cellular process essential for quality control of proteins, adaptation to stress and regulation of inflammation. As a defense mechanism, autophagy participates in controlling infections but also connects with antigen (Ag) presentation and thus activation of T cell responses.
HP1-dependent epigenetic regulation of T(reg) cell development and functions – EpiTreg
We will more precisely decipher the role of HP1 (Heterochromatin protein 1) and partners in the response of conventional and regulatory T cells to environmental signals and in the interplay between these two populations of cells. HP1s are non-histone chromosomal molecules that regulate genome functi
CommunitieS of paThOgens: a cRiminal conspiracY – STORY
Studies of infectious disease systems have typically tended to focus solely on the interaction between a host and a causative agent. This approach, inherited from medical methodology, has served epidemiologists well, especially for antigenically stable pathogens, such as measles or chickenpox. Howev
Stress responses and virulence in human fungal pathogens: a comparative systems biology approach of regulatory networks in Candida species – CANDIHUB
invasive fungal infections in humans. Systemic infections due to these yeasts are associated with high mortality rate despite the existing antifungal arsenal. Recent advances have been made in the functional genomics of these species with the development of collections of loss-of-function and gain-o
CX3CR1 and CX3CL1 in allergic diseases – CX3CR1
Allergic asthma is a T helper (Th) 2-dominated disease of the lung. In asthmatic patients, a fraction of CD4+ T cells express the CX3CL1 receptor CX3CR1, and its ligand CX3CL1 expression is increased in airway smooth muscle, lung endothelium and epithelium upon allergen challenge. In a recent study
Autoimmune mechanisms involved in narcolepsy with cataplexy – ImmunitySleep
Sleep is a fundamental neurological behavior for normal brain function. Sleep is a highly complex behavior regulated by many genes, environment, and gene-environment interactions. Sleep disorders are frequent with public health, socioeconomic and psychological consequences. Narcolepsy with cataplexy
Chikungunya Virus spread and interaction with the host – CHIKV-Viro-Immuno
CHIKV is a re-emerging mosquito-borne virus responsible for a severe, ongoing epidemic in the Indian Ocean region. It causes acute fevers and persistent arthralgia and myalgia. Little is known about the biology and pathogenesis of CHIKV. Our prior studies investigated viral replication and tropism,
EXploring T cell Activation Signal Integration in 4D – EXTASI 4D
Understanding signal integration is now a central challenge in immunology. To understand the induction of the adaptive immune response, new studies are necessary to reconcile our knowledge on TCR signaling mechanisms, learned from static experimental systems, with the dynamics of cell interactions d
Role of Zbtb24 and DNA methylation in late B-cell differention and humoral memory – METHYL-MEMORY
ICF patients display simultaneously an abnormal profile of DNA methylation and a primary humoral immune deficiency characterized by hypo-gammaglobulinemia and a deep decrease in the number of memory B cells. We want to elucidate the mechanistic link between the mutations that cause the ICF syndrome,
The Blood brain barrier: from bacterial meningitis to drug delivery into the CNS – NEMBRAIN
The blood-brain barrier (BBB) is the specialized system of brain microvascular endothelial cells that shields the brain from toxic substances in the blood, supplies brain tissues with nutrients, and filters harmful compounds from the brain back to the bloodstream. The unique barrier properties of th
Neuro-endocrine regulation of immunity – SensorImmune
Survival of organisms depends on their capacity to mount a defense against environmental agents that cause tissue damage and infection. The nervous system and the immune system are both involved in the detection of these “dangers” but they are traditionally thought of as serving separate functions.
Inborn errors of immunity to HSV-1 underlying childhood herpes simplex encephalitis: an exception or a rule? – IEIHSEER
Childhood herpes simplex virus 1 (HSV-1) encephalitis (HSE) is a devastating viral illness of unclear pathogenesis. HSE is the most frequent form of sporadic viral encephalitis in developed countries and affects otherwise healthy children with no relevant family history, unlike infectious conditions
Endogenous Gammaretroviral Envelope glycoproteins: Cell Metabolism Regulators or Infection Facilitators? – EndoGamER
Cross-species transmission of retroviruses is generally accompanied by mutational or recombinatory events that involve the envelope glycoproteins (Env). Seven genera of retroviruses infect vertebrates, of which the gammaretroviruses are the most abundant type in mammals. More than 15 Env of these ma
Deciphering the role of metals in mycobacterial virulence & host defence against tuberculosis – TB-MET
This project aimed: i) to elucidate the mechanism of action of several M. tuberculosis P-ATPases and their function in mycobacterial physiology and virulence in vitro and in vivo, ii) to identify potential inhibitors of M. tuberculosis P-ATPases and evaluate their potential as novel anti-TB drugs,
Functional and molecular characterization of Pandoraviruses – Pandoravirus
After our discovery of the largest giant virus Megavirus chilensis in 2011, following that of Mimivirus in 2003, we thought we had reached the ultimate limits in virion size and genome complexity. These viruses infecting Acanthamoeba largely encroach on a territory previously thought to be restricte
Deciphering tuberculosis pathogenesis by identifying single-gene inborn errors of immunity in severe childhood forms of the disease – TBPATHGEN
Tuberculosis (TB) remains a major public health problem. One fundamental although often neglected observation is that only a minority of individuals infected with Mycobacterium tuberculosis (Mtb) develop clinical TB. This phenomenon is largely unexplained, and the pathogenesis of TB therefore remain
Primary immunodeficiencies associated with susceptibility to Epstein Barr virus infection : studies from natural mutants to gene functions – IMMUNEBV
Epstein-Barr Virus (EBV) infection is one of the most powerful trigger of the immune system in humans causing severe pathologies including lymphoproliferative disorders. There are several known pediatric inherited immunodeficiencies leading to a susceptibility to EBV infection. These natural mutants
Type VI SecretBacterial warfare : Type VI Secretion System Architecture and Function – B-War
Bacteria do not live alone. When thriving in their environment, bacteria have to cope with many other species and therefore should collaborate or compete to access nutrients or to colonize more efficiently the ecological niche. It has been long known that pathogenic bacteria affect plants, animals a
Dynamics of the early steps of mammalian host infection by African trypanosomes – ENTRYPA
Human African Trypanosomiasis or sleeping sickness is a neglected tropical disease caused by the flagellated protist Trypanosoma brucei. Nagana is a similar disease in cattle due to closely related trypanosome species. The injection of these extra-cellular parasites by the bite of the tsetse fly ind
Specificity of secretory IgA and their impact on gut microbiota composition and host immunity. – METAntibody
Man has developed spectacular ways to protect himself from pathogens, while benefitting from unique and essential features of symbionts. Of note, bacteria acting as symbionts in one clinical setting may act as pathogens in another. Such bacteria are increasingly being referred to as “Pathobionts”. C
Genome-Wide Identification and Analysis of Coxiella-Host Interactions – AttaQ
Infectious diseases are among the leading causes of mortality and disability worldwide. Against a constant background of established infections, epidemics of emerging and re-emerging pathogens greatly aggravate the burden of infections on health and economy. Infections by bacterial pathogens depend