A5080468934- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cellular transport and secretion
- HIV-related health complications and treatments
- HIV/AIDS Research and Interventions
- Immune Response and Inflammation
- interferon and immune responses
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Complement system in diseases
- Cancer Immunotherapy and Biomarkers
- Glycosylation and Glycoproteins Research
- Adenosine and Purinergic Signaling
- Cytomegalovirus and herpesvirus research
- Lipid Membrane Structure and Behavior
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Erythrocyte Function and Pathophysiology
- Phagocytosis and Immune Regulation
- Mosquito-borne diseases and control
- Extracellular vesicles in disease
- Diabetes and associated disorders
Institut Curie
2015-2024
Inserm
2014-2024
Université Paris Sciences et Lettres
2016-2024
Immunité et Cancer
2008-2022
Institut National de Recherche en Santé Publique
2005
Institut Pasteur
1987-2001
Université Paris Cité
1999
Centre National de la Recherche Scientifique
1993-1999
Institut Cochin
1997
Massachusetts Institute of Technology
1993-1995
Exosomes are extracellular vesicles (EVs) secreted upon fusion of endosomal multivesicular bodies (MVBs) with the plasma membrane. The mechanisms involved in their biogenesis remain so far unclear although they constitute targets to modulate exosome formation and therefore a promising tool understand functions. We have performed an RNA interference screen targeting twenty-three components sorting complex required for transport (ESCRT) machinery associated proteins MHC class II (MHC...
The Drosophila (fruit fly) model system has been instrumental in our current understanding of human biology, development, and diseases. Here, we used a high-throughput yeast two-hybrid (Y2H)-based technology to screen 102 bait proteins from melanogaster , most them orthologous cancer-related and/or signaling proteins, against high-complexity fly cDNA libraries. More than 2300 protein-protein interactions (PPI) were identified, which 710 are high confidence. computation reliability score for...
Dendritic cells (DC) are professional antigen-presenting that orchestrate immune responses. The human DC population comprises two main functionally specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here, we combine high-dimensional technologies-single-cell messenger RNA sequencing (scmRNAseq) cytometry by time-of-flight (CyTOF)-to identify blood CD123+CD33+CD45RA+ precursors (pre-DC). Pre-DC share surface markers with plasmacytoid (pDC) but have...
Macrophages are important targets for HIV-1 infection and harbor the virions in an as yet unidentified organelle. To determine location of these cells, extensive analysis primary human macrophages infected vitro with was carried out by immuno-electron microscopy. Virus particles were found to accumulate intracellular multivesicular compartments which enriched major histocompatibility complex class II molecules CD63. These features characteristics where maturing acquire their peptide cargo....
HIV-1-infected cells can avoid cytotoxic T lymphocyte killing by Nef-mediated down-regulation of surface MHC I. Here, we show that HIV-1 Nef inhibits II restricted peptide presentation to specific and thus may affect the induction antiviral immune responses. mediates this effect reducing level mature (i.e., peptide-loaded) while increasing levels immature II, which are functionally incompetent because their association with invariant chain. was only gene product possess capacity, also...
Toll-like receptor (TLR) 3 is an endosomal TLR that mediates immune responses against viral infections upon activation by its ligand double-stranded RNA, a replication intermediate of most viruses. TLR3 expressed widely in the body and activates both innate adaptive systems. However, little known about how intracellular trafficking maturation are regulated. Here we show newly synthesized endogenous transported through ER Golgi apparatus to endosomes, where it rapidly cleaved. protein...
Here we describe a new mouse model that exploits the pattern of expression high-affinity IgG receptor (CD64) and allows diphtheria toxin (DT)-mediated ablation tissue-resident macrophages monocyte-derived cells. We found myeloid cells ear skin dermis are dominated by DT-sensitive, melanin-laden have been missed in previous studies correspond to ingested melanosomes from neighboring melanocytes. Those referred as melanophages humans. also identified melanocytic melanoma. Benefiting our...
Recently, it has been demonstrated that the human immunodeficiency virus type 1 (HIV-1) Nef from laboratory strains down-modulates cell surface expression of mature major histocompatibility complex class II (MHC-II) molecules, while up-regulating invariant chain (Ii) associated with immature MHC-II (P. Stumptner-Cuvelette, S. Morchoisne, M. Dugast, Le Gall, G. Raposo, O. Schwartz, and P. Benaroch, Proc. Natl. Acad. Sci. USA 98:12144-12149, 2001). These functions could contribute to impaired...
Clathrin and retromer have key functions for retrograde trafficking between early endosomes the trans-Golgi network (TGN). Previous studies on Shiga toxin suggested that these two coat complexes operate in a sequential manner. Here, we show curvature recognition subunit component sorting nexin 1 (SNX1) of interacts with receptor-mediated endocytosis-8 (RME-8) protein, RME-8 SNX1 colocalize together model cargo route, receptor-binding B-subunit (STxB). has previously been found to bind...
Major histocompatibility complex class I is down-regulated from the surface of human immunodeficiency virus (HIV)-1-infected cells by Nef, a virally encoded protein that thought to reroute MHC-I trans-Golgi network (TGN) in phosphofurin acidic cluster sorting (PACS) 1, adaptor (AP)-1, and clathrin-dependent manner. More recently, an alternative model has been proposed, which Nef uses AP-1 direct endosomes lysosomes. Here, we show knocking down either or clathrin with small interfering RNA...
During the late stages of HIV-1 replication cycle, viral polyprotein Pr55Gag is recruited to plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and directs assembly. We show that Rab27a controls trafficking endosomes carrying 4-kinase type 2 α (PI4KIIα) toward PM CD4+ T cells. Hence, promotes high levels 4-phosphate localized production PI(4,5)P2, therefore controlling association. also PI(4,5)P2 at virus-containing compartments macrophages. By screening...
The MHC class II-associated invariant chain interacts in trimeric form with II molecules, inhibits peptide binding, and mediates targeting of molecules to endosomal compartments. To dissect the different functions (Ii) chain, a set cDNAs, encoding truncated forms Ii was constructed. mRNAs, transcribed from these cDNAs were translated vitro, together mRNAs HLA DR1 alpha beta subunits. An truncation that contains 104 NH2-terminal amino acids able associate molecules. This construct region...
Newly synthesized MHC II alpha- and beta-chains associated with the invariant chain chaperone (Ii) enter endocytic pathway for Ii degradation loading peptides before transport to cell surface. It is unclear how alphabetaIi complexes are sorted from Golgi apparatus directed endosomes. However, indirect evidence tends support direct involving AP1 clathrin adaptor complex. Surprisingly, we show here that knocking down production of by RNA interference did not affect trafficking complexes. In...
HIV type 1 (HIV-1) infects CD4(+) T lymphocytes and tissue macrophages. Infected macrophages differ from cells in terms of decreased to absent cytopathicity for active accumulation new progeny HIV-1 virions virus-containing compartments (VCC). For these reasons, infected are believed act as "Trojan horses" carrying infectious particles be released on cell necrosis or functional stimulation. Here we explored the hypothesis that extracellular ATP (eATP) could represent a microenvironmental...
The human dendritic cell (DC) lineage has recently been unraveled by high-dimensional mapping, revealing the existence of a discrete new population blood circulating DC precursors (pre-DCs). Whether this possesses specific functional features as compared to other subset upon pathogen encounter remained be evaluated. A unique feature pre-DCs among DCs is their constitutive expression viral adhesion receptor Siglec-1. Here, we show that pre-DCs, but not subsets, are susceptible infection HIV-1...