Search
Molecular mechanisms of spirochetal motility: the endoflagellum of Leptospira as a working model – LEPTOMOVE
LEPTOMOVE seeks to decipher the molecular mechanims of motility of spirochetes, which includes major pathogens such as the agents of leptospirosis, syphilis and Lyme disease. Despite its proven critical importance for pathogenesis, the molecular architecture of the spirochete’s flagellum, which is a
Plasmodium vivax Invasion Pathways into Human Reticulocytes – VIPeRs
P. vivax remains a major public health problem in developing countries. Like the other Plasmodium species, P. vivax has a complex life cycle involving multiple stages in the mosquito vector and human host. For instance, erythrocyte invasion is a complex process involving multiple interactions betwee
Malaria Infectious Reservoir and Genomics: in search of elusive malaria parasites in the dry season – MIRaGe
In Project 1, using parasite whole genome sequences collected all year round, we will test the hypothesis that the dry season induces a bottleneck on the parasite genetic diversity. In Project 2, we will address the question whether the parasite is able to sense its environment and adapt to it.
B cell signaling and Early Plasma Cell Fate Decision – CascadingPCdiff
The proposal attempts to identify key steps and key targets in the transition from naive B cells through to plasma cells. It will be conducted on two levels: first an experimental approach in mice models to study the role of IL-2/IL-15 signalling in B cell fate decision. Indeed, accumulated evidence
Role of Type IV pilus retraction in bacterial pathogenesis – RETRACTOPATH
Neisseria meningitidis (meningococcus) is a bacterium responsible for septicaemia and meningitis in humans. It interacts with vascular cells via its Tfp and promotes the formation of purpuric lesions often evolving towards a fatal outcome. The overall objective of this proposal is to decipher the
Characterization of commensal-mediated immune education in mouse and its relevance for humans – MicroEducation
Within the hundreds of species that comprise the bacterial gut microbiota, studies in mice have shown that SFB play a privileged role in inducing a unique state of physiological inflammation in the gut that protects the host from a wide range of pathogens. However, the molecular details of how SFB i
Contribution of Type VI Secretion System Effectors in Adherent Invasive Escherichia coli pathogenicity – EffAIECTS
Numerous studies have confirmed mucosal association of AIEC (between 21 to 63% of CD patients) in various cohorts of CD patients. AIEC strains are able to adhere to and invade intestinal epithelial cells, to survive and replicate within macrophages and colonize ileal gut mucosa in CD patients. The c
Beneficial host - microbiota symbiosis upon chronic undernutrition: Commensal Bacteria Envelope and Host Linear Growth Promotion – SymEnvLop
Drosophila is a powerful host model for coupling functional genetics and genomic studies with integrative physiology. We have previously demonstrated that upon chronic undernutrition, mono-association of germ-free Drosophila larvae with a single strain of the dominant natural fly gut commensal bacte
Role of three-dimensional chromatin organization and spatial co-localization during B to plasma cell differentiation – PLASMADIFF-3D
The “PLASMADIFF-3D” project (36 months, 2 teams) addresses scientific issues pertinent to the B-cell-lineage and their implications in immunopathology, with specific focus on antibody-secreting plasma cells. The main objectives of our project are: - Characterize the epigenome modifications during
Deciphering Legionella pneumophila induced epigenetic modifications: characterization of a prokaryotic histone deacetylase – LEGENhD
Legionellosis is an important human disease present in 1 to 5% of community-acquired pneumonia with a high mortality rate (11% to 33%), in particular for immunocompromised and elderly people. Its causative agent, Legionella pneumophila is an intracellular pathogen that co-evolved with eukaryotic hos
Deciphering tolerance breakdown in a human B-cell mediated autoimmune disease – Autoimmuni-B
(1) Does the reappearance of autoantibodies during disease relapses originate from the residual memory B cells that have survived the B cell depleting treatment, or do they come from newly formed naïve B cells? (2) At what step of B cell development does the tolerance breakdown against platelet ant
TLR7 at the interface of obesity and metabolic syndrome – TollSOME
Evaluation of the contribution of TLR7 signaling in the development of high fat diet induced obesity and metabolic syndrome by studying the weight gain and metabolic phenotype inTLR8ko (increased expression of TLR7 by dendritic cells), TLR7/8ko or TLR7ko (absence of TLR7 signaling) and littermate wi
Unravelling the biology of African trypanosomes in the skin – TrypaDerm
Trypanosoma brucei gambiense causes chronic Human African Trypanosomiasis (gHAT). These extra-cellular protist parasites are transmitted by tsetse flies and proliferate in the host blood. We have recently demonstrated that the skin was a major yet overlooked anatomical reservoir for trypanosomes tha
Meningococcal Infections-on-Chip: Integration of the Tissue Architecture – MeningoChip
Dissemination of pathogenic microorganisms throughout the organism relies on their ability to cross biological barriers. Neisseria meningitidis (Nm) is a human-restricted bacterium responsible for sepsis and meningitis although the bacterium is commonly found as a commensal of the human nasopharynx
Lifelong Persistence Strategies of Toxoplasma gondii : Conquering the Host Cell and Evading Innate Immunity – HostQuest
The ancient phylum Apicomplexa includes many of the world’s pre-eminent protozoan pathogens. Most deadly to humans is Plasmodium, the agent of malaria, which kills around a million people annually. As obligate intracellular parasites, they establish intimate interactions with their hosts. Toxoplasma
Composition, stoichiometry, dynamics, and spatial organization of the CD28 costimulatory pathway of primary T cells triggered by physiological stimuli – SUPER-BASILIC
Although the T cell antigen receptor occupies a central place in T cell physiology, it does not work in isolation and the signals it delivers are enhanced by costimulatory molecules such as CD28. We recently identified a novel intracytoplasmic protein called RLTPR that is essential for CD28 costimul
Host susceptibility factors to pediatric encephalitis in South East Asia – SEAe-HostFactors
Infectious encephalitis is of public health concern worldwide, given its high mortality and neurological sequelae rates. Reported incidences range between 3.5 and 7.4 cases per 100,000 patient years, with higher incidences in children than adults, and in Asia than other parts of the world. Southeast
MHC I Ag presentation by Central nervous system-resident cells during Chronic infection of the Brain – MICCHROB
Rather than being ‘immune-privileged’, the brain is endowed with a unique immunological status, including innate and adaptive mechanisms that are essential for the detection and control of neurotropic infections. It is now established that Major Histocompatibility Complex class I (MHC I) molecules
Epigenetics of viral persistence induced by the association of latent herpes simplex virus 1 with promyelocytic leukemia nuclear bodies (PML-NBs) – EPIPRO
The comprehension of the molecular mechanisms that contribute to the establishment and then maintenance of a persistent virus in its lethargic state is essential to understand the reasons for the resurgence of the associated disease once the virus reactivates. The EPIPRO project is designed to under
Cellular and Molecular Requirements for Extracellular Vesicle-mediated Antigen Delivery to Dendritic Cells – EVUp
Extracellular vesicles (EVs) serve a direct role in intercellular communication by sampling the biochemical content (such as RNAs and proteins) in a donor cell and transferring the sample to an acceptor cell. Little is known of the delivery process of EVs to the recipient cells. This stands in contr
How does microbiota-born peptidoglycan affect host homeostasis? – Peptimet
A universal feature of organisms with open digestive tracts is colonization of the gastrointestinal tract by a characteristic commensal microbiota. This microbiota, which thrives on the nutrients produced by host’s diet, is shaped by host-specific selective pressures such as the intestinal environme
New signalling pathways involved in hemophagocytic lymphohistiocytic syndrome – newHLH
Hemophagocytosis lymphohistiocytosis (HLH) is an early onset lymphoproliferative and hyperinflammatory syndrome characterized by tissue infiltration by activated polyclonal T lymphocytes and macrophages. Over the years, we and others have greatly contributed to establish the relation between genetic
Reshaping the microbiota of mosquitoes to study its impact on malaria transmission – MosMi
Malaria vectors can only transmit malaria after getting infected when biting infectious people. The mosquito microbiota protects its host against infection by parasites and negatively affects the mosquito fitness, impacting the chance of transmission. So far, functional studies on the microbiota hav
Exploring the immunological basis for gender differences in susceptibility to TB – GENDER-TB
Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (M. tuberculosis), is responsible for more than 1.8 million deaths worldwide. Males are affected roughly twice as much as females by TB, both in terms of cases and deaths. It is tempting to speculate that such discrepancy between
Characterization of mitochondrial and ER dynamics during Brucella infection – charM-Ed
Many bacterial pathogens can highjack the endoplasmic reticulum (ER) to promote intracellular replication. This is the case of Brucella spp., which uses a type IV secretion system (T4SS) to sustain interactions with the ER enabling formation of a replicative compartment. Brucella infection has been
Understanding the biology and physiopathology of CTPS1, a novel target for the development of immunosuppressive drugs. – ImmunoBioCTPS1
We recently reported a novel combined immunodeficiency in patients with loss of function mutations in the CTPS1 gene and characterized by high susceptibility to viral infection due to inability of T cell to proliferate and control infections. The project aims at acquiring fundamental knowledge on th
Contribution of ILC and CD8 to Non-Alcoholic SteatoHepatitis and progression towards hepatocarcinoma – NASHILCCD8
CONTEXT. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western countries. It represents a continuum encompassing stages ranging from isolated steatosis to non-alcoholic steatohepatitis (NASH), characterized by lobular inflammation and ballooning, with or witho