Search

NKT cells develop in the thymus, and branch away from the conventional aß T cells at the DP stage, upon positive selection by adjacent CD1d-expressing cortical DP. TCR signals are a hallmark of NKT cell positive selection, and likely drive their effector memory phenotype and innate effector program.

Bacterial respiratory tract infections are a major cause of morbidity and mortality in older adults. Circadian rhythms regulate a wide variety of physiological, metabolic, and immune processes. Circadian rhythms are disrupted in the elderly, predisposing them to diseases. Our data in elderly mice in

Fever is a cardinal feature of inflammation. Global elevation in body temperature can have direct effects on pathogens and can also act more indirectly by boosting immune responses. Besides the global elevation of temperature, focal increases of temperature are also recorded at inflammatory sites, a

Interestingly, among several phenotypic traits, STING GOF mice develop a severe combined immunodeficiency (SCID) phenotype (T, B and NK lymphopenia). In addition, we demonstrated that B- and T-cell developmental blockade in STING GOF mice originates at early stages in the bone marrow (BM) and the th

The project aims at providing an understanding of antibody-mediated neutralization of Plasmodium sporozoites. To do so we will (1) test the generality of the skin-dependent protective mechanism of cytotoxic anti-circumsporozoite (CSP) antibodies using sporozoites expressing the CSP of rodent-infecti

HAUSP has multiple roles in regulating the p53–MDM2 pathway during virus-induced tumor cell survival and appears to be an important target that pathogens must circumvent. It is currently unknown how GRA16 affects HAUSP activity to explain its effect on the p53 pathway. However, the simplest explanat

Open Questions Mf and MCs are the most abundant resident immune cells in the skin. Although the skin also harbors several populations of T cells, Mf and MCs are the only cell types occupying the perivascular space at steady state. This unique perivascular positioning raises several important questi

Colon cancer (CC) represents a challenging conundrum for immunologists. The prognosis for patients suffering from CC strongly relies on tumor infiltrating lymphocytes including T follicular helper cells (TFH), but also chemotherapy-induced immune responses. Importantly, although successfully applied

Viral replication takes place in specific compartments called viral factories (VF). Their physicochemical nature and the molecular basis of their morphogenesis and organization are poorly understood. The VFs of RABV are the bodies of Negri (NB) that are cytoplasmic inclusions harboring the synthesi

Type I interferon (IFN-I) is critical for protection against viral infections. The plasmacytoid dendritic cells (pDCs) are robust IFN-I producers. This involves the recognition of viral nucleic acids by endolysosome-localized sensors (TLR7 and TLR9). Nonetheless, pDCs are refractory to virtually all

We aim to understand the role of bladder tissue resident macrophages in homeostasis and disease. Objective 1. Delineate the role of bladder-resident M? subsets during homeostasis, UTI, and resolution. Objective 2. Uncover the ontogeny and the mechanisms of homeostatic renewal of bladder M? subs

Recent work has identified transposable elements (TE) as a putative source of cis-regulatory regions in myeloid cells. In line with this notion, we recently showed that a limited repertoire of endogenous retroviruses (ERV) has been exapted into a network of cis-regulatory modules that shape and cont

The phylum Apicomplexa includes parasitic protists such as Toxoplasma and Plasmodium that cause devastating diseases in humans and farm animals. The acute phase of toxoplasmosis (the disease caused by Toxoplasma), is due to a fast replication and dissemination of the tachyzoite stage, which is usual

Cellular homeostasis requires permanent cellular surveillance and response to internally and externally inflicted insults. Such insults include the DNA damage response (DDR) and the unfolded protein response (UPR) directed against DNA or protein damage e.g. caused by invading pathogens. Membrane dam

CD8 T cells are essential to eliminate pathogen-infected cells or tumors. During an acute pathogen infection, CD8 T cells undergo a phase of contraction following pathogen clearance leaving a small number of memory CD8 T cells persisting over time. By contrast antigen persistence and chronic inflamm

Recognition of cytosolic DNA by the innate sensor cGAS is critical for activation of immune responses during bacterial & viral infections. cGAS also recognizes DNA released in the cytosol following nuclear & mitochondrial damages, leading to senescence and inflammation. This role of cGAS in a normal

The major objective of this project is to investigate the cellular function of new PBP regulators in the assembly of the bacterial cell wall using two different gram-positive bacterial models. In addition, we will also test if these regulators can affect bacterial resistance to ß-lactam antibiotic

The fundamental objective of MacrophageDynamics project is to 1/ set up original tools to study if and how macrophages switch phenotypes in a living organism, which so far has proven difficult to observe in vivo and 2/ discover new mechanisms involved in the phenotype switch of macrophages during an

Trypanosoma brucei, the causative agent of HAT, was believed to spread exclusively in the fluids of its mammalian host. Breaking with this dogma, we recently shown that most parasites reside in the extravascular compartment, in particular the skin and adipose tissue, where they are in close contact

The cellular chromatin is dynamic structure capable of switching from a condensed to a more open state and vice versa. This transition involves intrinsic nucleosome determinants; on the one hand the N terminal tail of histone H4 and the H2A/H2B acidic patch. The binding of one H4 tail to the neighbo

While investigating the mechanism of resistance in this tissue, we observed that 7 accessory/supernumerary subunits of complex I of the mitochondrial respiratory chain are differentially expressed between DENV resistant and susceptible mosquitoes. The function of these supernumerary subunits remains

Antibodies (Ab) are essential for efficient and long-term protection against infection. They are produced by plasma cells (PCs) corresponding to the last stage of B cell differentiation and play an essential part in host protection and tissue homeostasis directly by neutralizing pathogens but also b

The mechanisms by which IRAP controls FcR activation and how these impacts diseases are unknown and will be investigated by the 4 working packages of the IDEA project: WP1. Understand the molecular mechanisms by which IRAP facilitates FcgR activation : This WP will include cellular biology method

B cells are the main cells of the adaptive immune response being able, after contact with an antigen, to differentiate into antibody-producing effector cells, plasma cells (PC), or memory B cells which provide a rapid response in case of second contact with the antigen. Understanding the B cell diff

Aberrant regulation of the inflammatory response is highly suspected in numerous cancers and chronic inflammatory diseases. NF-kB transcription factors are key actors in the transcriptional cascade leading to inflammation, they activate genes with pro- or anti-inflammatory activities. Massive effort

It has long remained elusive how the central nervous system (CNS) fends off a variety of viral infections. We demonstrated that forebrain HSV1 encephalitis of childhood can result from monogenic deficiencies of TLR3-IFN-mediated CNS-intrinsic immunity. We recently discovered autosomal recessive defi

Malaria is caused by parasites of the genus Plasmodium. Whilst the disease is caused by asexual parasites, only sexual forms are capable of transmitting the infection to mosquitoes. Sexual forms arise from a small subset of blood-stage parasites which divert from the cycle of asexual replication and

Bacteria growing as surface-attached communities called biofilms are characterized by extensive physiological changes leading to the expression of different properties in comparison to planktonic bacteria. Among the properties induced by reduced diffusion and physico-chemical heterogeneity prevailin

Autoimmune type 1 diabetes (T1D) is characterized by pancreatic islet inflammation (insulitis) and destruction of insulin-producing beta cells. This destruction involves the recognition of peptide-HLA Class I (pHLA-I) complexes on the beta-cell surface by autoreactive CD8+ T cells. We identified the

Pathogenic mycobacteria have evolved a remarkable ability to evade the immune system and to colonize and survive within the host. Among the key evasion strategies is the capacity of these bacteria to parasitize host macrophages, which represent the major effector cells against intracellular pathogen

Mucosal Associated Invariant T cells (MAIT) are an evolutionary conserved subset recognizing vitamin B2 metabolites presented by the MHC class Ib molecule, MR1. MAIT cells have emerged as a key T cell subset because of their wide anti-microbial specificity, high inter-species conservation and abunda

Our objectives are: 1) to investigate whether cells bearing heterozygous pathogenic variants in mitochondrial genes will develop mitochondria dysfunction and important transcriptomic changes in the presence of IFN?/TNFa 2) to investigate whether cells bearing heterozygous pathogenic variants will in

Chronic obstructive pulmonary disease (COPD), primarily caused by cigarette smoking (CS), is punctuated by life-threatening clinical exacerbations mainly elicited by bacterial or viral infections. The underlying mechanisms and mediators that drive the induction of inflammation leading to chronic inf