Denis Hudrisier

Denis Hudrisier
French National Centre for Scientific Research | CNRS · Institute of Pharmacology and Structural Biology

PhD

About

73
Publications
28,527
Reads
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3,462
Citations
Introduction
I have been working for years on several aspects of T cell biology: i) role of allele-specific motifs in antigen binding to MHC ii) serial TCR engagement in T cell activation and iii) trogocytosis (http://en.wikipedia.org/wiki/Trogocytosis). Recently I became interested in studying the adaptive immune response against Mycobacterium tuberculosis in Olivier Neyrolles'lab in Toulouse. PLEASE VISIT http://denhud-iloveimm.blogspot.fr/ & http://www.scoop.it/t/immunology-vaccine-infectious-diseases
Additional affiliations
May 2009 - present
CNRS and Paul Sabatier University
Position
  • Professor in Immunology
Description
  • Adaptive immune response to tuberculosis
July 2008 - September 2008
BT-Pharma
Position
  • Consultant
July 2004 - May 2009
INSERM, CNRS and Paul Sabatier University
Position
  • Associate Professor in Immunology
Description
  • Molecular mechanisms and biological significance of trogocytosis
Education
September 1993 - July 1996
September 1992 - July 1993
Paul Sabatier University - Toulouse III
Field of study
  • Immunopharmacology
September 1990 - September 1991
Paul Sabatier University - Toulouse III
Field of study
  • Biochemsitry

Publications

Publications (73)
Article
Full-text available
The granuloma is an elaborated aggregate of immune cells found in non-infectious as well as infectious diseases. It is a hallmark of tuberculosis (TB). Predominantly thought as a host-driven strategy to constrain the bacilli and prevent dissemination, recent discoveries indicate the granuloma can also be modulated into an efficient tool to promote...
Article
Full-text available
Tuberculosis (TB), caused by the airborne bacterial pathogen Mycobacterium tuberculosis, remains a major source of morbidity and mortality worldwide. So far, the study of host-pathogen interactions in TB has mostly focused on the physiology and virulence of the pathogen, as well as, on the various innate and adaptive immune compartments of the host...
Data
Microbiota dysbiosis does not alter immune cell populations in the lungs. (A) The total numbers of F4/80+CD11c+ macrophages, CD11c+MHCII+ dendritic cells, CD11b+GR1hi neutrophils, CD3−NK1.1+ NK cells, CD3+CD4+ T lymphocytes and CD19+ B cells were quantified by flow cytometry in lung homogenates from uninfected ABX vs. non-ABX mice. (B) Cytometry an...
Data
Microbiota dysbiosis does not alter innate myeloid and lymphoid cell populations during early lung colonization by M. tuberculosis. The total number of F4/80+CD11c+ macrophages, CD11c+MHCII+ dendritic cells, CD11b+GR1hi neutrophils, and CD3−NK1.1+ NK cells were quantified by flow-cytometry in lung homogenates from M. tuberculosis-infected ABX vs. n...
Data
NKT and γ/δ T cells are not modified in infected microbiota-altered mice. (A) Gating strategy to analyze unconventional innate-like lymphocytes, namely NKT cells (CD3+NK1.1+) and γ/δ T cells (CD3+TCRγ/δ+) by flow cytometry. (B,C) (B) Total NKT cells (left) and γ/δ T cells (right) and (C) percentages in the lungs of control (non-ABX) and ABX mice 7...
Data
Antibodies used in the study for flow cytometry.
Data
Microbiota dysbiosis does not impact early inflammatory response to M. tuberculosis infection in lungs. (A) The expression of inflammatory cytokines and the antimicrobial peptide CRAMP was measured by RT-qPCR in the lungs of non-ABX vs. ABX mice 7 days p.i., Gene expression represents relative Ct value compared to Hprt Ct value (ΔCt) and the mean o...
Data
Primers used in the study for RT-qPCR.
Article
Full-text available
Rationale: In addition to their well-known function as antibody-producing cells, B lymphocytes can markedly influence the course of infectious or non-infectious diseases via antibody-independent mechanisms. In tuberculosis, B cells accumulate in lungs, yet their functional contribution to the host response remains poorly understood. Objectives:...
Article
Full-text available
Immune response against pathogens is a tightly regulated process that must ensure microbial control while preserving integrity of the infected organs. Tuberculosis (TB) is a paramount example of a chronic infection in which antimicrobial immunity is protective in the vast majority of infected individuals but can become detrimental if not finely tun...
Article
In tuberculosis, antigens are transferred from infected to uninfected dendritic cells. Does this favor T lymphocyte response and anti-mycobacterial host defense? In a recent report published in Cell Host & Microbe, Ernst and colleagues show that Mycobacterium tuberculosis seems to have hijacked this mechanism for its own benefit.
Article
Full-text available
Understanding the molecular components of immune recognition of the tuberculosis (TB) bacillus, Mycobacterium tuberculosis, can help designing novel strategies to combat TB. Here, we identify collectin CL-LK as a novel soluble C-type lectin able to bind M. tuberculosis, and characterize mycobacterial mannose-capped lipoarabinomannan as a primary li...
Article
The importance of CD4 T lymphocytes in immunity to M. tuberculosis is well established; however, how dendritic cells activate T cells in vivo remains obscure. In this issue of Cell Host & Microbe, Srivastava and Ernst (2014) report a mechanism of antigen transfer for efficient activation of antimycobacte-rial T cells. Due to their unique ability to...
Article
Le systeme trimoleculaire constitue du recepteur des lymphocytes T (TCR), du peptide antigenique et de la proteine du complexe majeur d'histocompatibilite (CMH) est au centre des relations entre les cellules cibles et les cellules effectrices du systeme immunitaire. Grâce aux connaissances acquises ces dernieres annees sur les interactions CMH-pept...
Article
Full-text available
The pattern of receptors sensing pathogens onto host cells is a key factor that can determine the outcome of the infection. This is particularly true when such receptors belong to the family of pattern recognition receptors involved in immunity. Mycobacterium tuberculosis, the etiologic agent of tuberculosis interacts with a wide range of pattern-r...
Article
Full-text available
CD8(+) T cells have been shown to capture plasma membrane fragments from target cells expressing their cognate antigen, a process termed "trogocytosis". Here, we report that human CD4, the Human Immunodeficiency Virus (HIV) receptor, can be found among the proteins transferred by trogocytosis. CD4 is expressed in a correct orientation after its cap...
Article
Full-text available
Exchange of plasma membrane fragments, including cell-surface proteins and lipids, in conjugates formed between lymphocytes and their cellular partners is a field of intense investigation. Apart from its natural occurrence during Ag recognition, the process of membrane transfer can be triggered in experimental or therapeutic settings when lymphocyt...
Data
Differences in the transfer efficiency of various GFP proteins on T or B cells are not correlated to their expression levels at the PM. A) A mask (middle panel) delimitating the PM of HEK-FcRγGFP was constructed using the Metamorph software based on extra-cellular anti-MHC class I staining (left panel) and was applied on FcRγ-GFP staining in order...
Data
Examples of the levels of expression attained after transient transfection with plasmids coding for various proteins fused to GFP. Typical examples of flow cytometry analyses 48 hours after transient transfection in HEK-FcγRII of 9 different proteins fused to GFP. This type of analysis was performed systematically for all proteins used in this stud...
Data
The transfer efficiency of a given protein by trogocytosis is not directly related to its level of expression by target cells. A) Expression by HEK-FcγRII cell of the FcRγ-GFP protein expressed after transient transfection with increasing amounts of vector encoding FcRγ-GFP is shown in the top panels. Capture of the FcRγ-GFP by gated OT-I cells exp...
Article
Full-text available
T and B cells capture antigens via membrane fragments of antigen presenting cells (APC) in a process termed trogocytosis. Whether (and how) a preferential transfer of some APC components occurs during trogocytosis is still largely unknown. We analyzed the transfer onto murine T and B cells of a large panel of fluorescent proteins with different int...
Article
Full-text available
Intercellular transfer of cell surface proteins by trogocytosis is common and could affect T cell responses. Yet, the role of trogocytosis in T cell function is still elusive, and it is unknown whether a molecule, once captured by T cells, harbors the same biological properties as in donor APC. In this study, we showed that FcgammaR as well as the...
Article
T cells acquire various proteins from their cellular partners by the process of trogocytosis. We recently demonstrated that the FcγRIIIA receptor and its associated FcRγ are captured by T cells during their co-culture with FcγR-expressing target cells upon both antigen- or antibody-mediated stimulation. Interestingly, we found that FcR captured by...
Article
Full-text available
T cells acquire various proteins from their cellular partners by the process of trogocytosis. We recently demonstrated that the FcγRIIIA receptor and its associated FcRγ are captured by T cells during their co-culture with FcγR-expressing target cells upon both antigen- or antibody-mediated stimulation. Interestingly, we found that FcR captured by...
Article
Vaccination with recombinant adenylate cyclase of Bordetella pertussis (CyaA) carrying antigen is a promising approach to target antigen-presenting cells. We have used Trogocytosis Analysis Protocol (TRAP) assays to monitor immune responses raised by different vaccination regimens with recombinant CyaA carrying the ovalbumin antigen. We find that t...
Article
Trogocytosis is a recently discovered phenomenon whereby lymphocytes capture fragments of the plasma membrane from antigen presenting cells (APCs). Using APCs labeled with widely used fluorescent lipophilic probes, we previously described a trogocytosis analysis protocol (TRAP) useful to understand the mechanisms and biological consequences of this...
Article
Compared with cell-free viral infection, virological synapses increase HIV capture by target cells, viral infectivity and cytopathicity, and are believed to be less sensitive to antibody neutralization. We have evaluated the impact of antibodies against HIV envelope glycoproteins (gp120 and gp41) on cell-to-cell HIV transmission. We analyzed the ro...
Article
Full-text available
Upon recognition of their respective cellular partners, T and B cells acquire their antigens by a process of membrane capture called trogocytosis. Here, we report that various inhibitors of actin polymerization or of kinases involved in intracellular signaling partially or fully inhibited trogocytosis by CD8(+) and CD4(+) T cells, whereas they had...
Article
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A major challenge in transplantation medicine is controlling the very strong immune responses to foreign antigens that are responsible for graft rejection. Although immunosuppressive drugs efficiently inhibit acute graft rejection, a substantial proportion of patients suffer chronic rejection that ultimately leads to functional loss of the graft. I...
Article
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The main function of regulatory T lymphocytes is to keep autoimmune responses at bay. Accordingly, it has been firmly established that the repertoire of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) is enriched in autospecific cells. Differences in thymic-positive and/or -negative selection may account for selection of the qualitatively distinct...
Article
Full-text available
Multiple sclerosis (MS) is a demyelinating inflammatory disease of the CNS. Though originally believed to be CD4-mediated, additional immune effector mechanisms, including myelin-specific CD8(+) T cells, are now proposed to participate in the pathophysiology of MS. To study the immunologic and encephalitogenic behavior of HLA-A*0201-binding myelin-...
Article
Cytotoxic T lymphocytes recently stimulated by antigen-presenting cells (APC) display major histocompatibility class (MHC) I and II molecules inherited from APC. We have previously reported that, in vitro, transfer of MHC molecules and several other proteins occurs through trogocytosis, i.e. the active acquisition of target cell membrane fragments...
Article
Full-text available
Key events of T and B cell biology are regulated through direct interaction with APC or target cells. Trogocytosis is a process whereby CD4(+) T, CD8(+) T, and B cells capture their specific membrane-bound Ag through the acquisition of plasma membrane fragments from their cellular targets. With the aim of investigating whether the ability to trigge...
Article
Full-text available
Trogocytosis, the process whereby lymphocytes capture membrane components from the cells they interact with, is classically evidenced by the transfer of fluorescent lipophilic compounds or biotinylated proteins from target cells to T or B cells. A particular class of molecules, not studied explicitly so far in the context of trogocytosis is glycoco...
Article
Full-text available
Detection, quantification, separation and characterization of T and B cells reactive to specific antigens are important tasks in both basic and clinical immunology. Here, we describe an approach allowing the performance of all four tasks on a functional basis by flow cytometry. The assay is based on the property of lymphocytes to capture membrane c...
Article
Full-text available
We have developed a method exploiting the phenomenon of trogocytosis to detect lymphocytes reacting specifically with target cells by flow cytometry. Trogocytosis is a process by which lymphocytes capture fragments of the plasma membrane from the antigen-presenting cells (APCs) expressing their cognate antigen. For this method, a label (such as a f...
Article
Full-text available
We coined the word trogocyto-sis from the ancient greek trogo which means nibble (1). It refers to a cellular process whereby a recipient cell rapidly and actively 'nibbles' sizeable quantities of plasma membrane fragments from a donor cell following spe-cific receptor-ligand interactions. This mechanism explains how some recipient cells can captur...
Article
Full-text available
Natural CD4+CD25+ regulatory T lymphocytes (Treg) are key protagonists in the induction and maintenance of peripheral T cell tolerance. Their thymic origin and biased repertoire continue to raise important questions about the signals that mediate their development. We validated analysis of MHC class II capture by developing thymocytes from thymic s...
Article
We have investigated the density of peptides required to elicit different biological responses in cytotoxic T lymphocytes (CTL), including trogocytosis (i.e., the phenomenon whereby the lymphocytes actively capture fragments of plasma membrane from those cells with which they establish an immune synapse). We have used two separate mouse models of C...
Article
Full-text available
Thymus-derived regulatory T lymphocytes of CD4(+)CD25(+) phenotype regulate a large variety of beneficial and deleterious immune responses and can inhibit lethal graft-versus-host disease in rodents. In vitro, CD4(+)CD25(+) T cells require specific major histocompatibility complex (MHC)/peptide ligands for their activation, but once activated they...
Article
Full-text available
Several reports have documented that lymphocytes can extract surface molecules through the 'immunological synapse' from the antigen-presenting cells to which they are conjugated1. This phenomenon, which we have called 'trogocytosis'1 (from the ancient Greek trogo, meaning 'gnaw'), involves the transfer of plasma membrane fragments from the presenti...
Article
Full-text available
Recognition by CD8+ cytotoxic T lymphocytes (CTLs) of antigenic peptides bound to major histocompatibility class (MHC) I molecules on target cells leads to sustained calcium mobilization and CTL degranulation resulting in perforin-dependent killing. We report that beta1 and beta3 integrin-mediated adhesion to extracellular matrix proteins on target...
Article
Full-text available
Recognition by CD8+ cytotoxic T lymphocytes (CTLs) of antigenic peptides bound to major histocompatibility class (MHC) I molecules on target cells leads to sustained calcium mobilization and CTL degranulation resulting in perforin-dependent killing. We report that β1 and β3 integrin-mediated adhesion to extracellular matrix proteins on target cells...
Article
Full-text available
Occasional EBV infection of human NK cells may lead to malignant diseases such as naso-pharyngeal NK lymphoma although NK cells do not express CD21, the primary receptor for EBV. Here we show that during early EBV infection in patients, NK cells attacked EBV-infected autologous B cells. In vitro, NK cells activated by conjugation to CD21(+) B-EBV c...
Article
The T-cell repertoire developing in the thymus is rid of autospecific cells by the process of thymic negative selection. Recognition of major histocompatibility complex (MHC)/self-peptide complexes expressed by thymic antigen-presenting cells (APC) of bone marrow origin leads to induction of apoptotic death of autospecific thymocytes. Induction of...
Article
Full-text available
B, alpha beta T, and NK lymphocytes establish immunological synapses (IS) with their targets to enable recognition. Transfer of target cell-derived Ags together with proximal molecules onto the effector cell appears also to occur through synapses. Little is known about the molecular basis of this transfer, but it is assumed to result from Ag recept...
Article
Prior to delivery of a lethal hit, NK cells form an immunological synapse to scan the target cells and engage their activatory and inhibitory receptors. Using freshly isolated NK cells, IL-2-activated polyclonal NK bulk or the NKL cell line, we report here that early during this recognition process, human NK cells actively capture target cell membr...
Article
Full-text available
Upon physiological stimulation, receptors with tyrosine kinase activity (RTK) are rapidly internalized together with their soluble ligands. T cell activation is the consequence of recognition by the T cell receptor (TCR) of specific peptide-major histocompatibility protein complexes (peptide-MHC) present at the membrane of antigen-presenting cells...
Article
Full-text available
T cell tolerance to self Ags is in part established in the thymus by induction of apoptosis or anergy of potentially autoreactive thymocytes. Some autospecific T cells nevertheless migrate to peripheral lymphoid organs but are kept under control by the recently identified CD4(+)CD25(+) regulatory T cell subset. Because these cells inhibit autoimmun...
Article
Full-text available
Integral membrane proteins can't pass from the surface of one cell to that of another – or can they? Cells of the immune system that form a tight 'synapse' with their target cells clearly do acquire chunks of plasma membrane, leaving their targets a little nibbled at the edges, but otherwise unharmed. Over the past two years, several reports have d...
Article
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The fate of viral glycopeptides as cytotoxic T lymphocyte (CTL) epitopes is unclear. We have dissected the mechanisms of antigen presentation and CTL recognition of the peptide GP392-400 (WLVTNGSYL) from the lymphocytic choriomeningitis virus (LCMV) and compared them with those of the previously reported GP92-101 antigen (CSANNSHHYI). Both GP392-40...
Article
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Structural similarity (molecular mimicry) between viral epitopes and self-peptides can lead to the induction of autoaggressive CD4+ as well as CD8+ T cell responses. Based on the flexibility of T cell receptor/antigen/major histocompatibility complex recognition, it has been proposed that a self-peptide could replace a viral epitope for T cell reco...
Article
Full-text available
Upon encounter of a CTL with a target cell carrying foreign Ags, the TCR internalizes with its ligand, the peptide-MHC class I complex. However, it is unclear how this can happen mechanistically because MHC molecules are anchored to the target cell's surface via a transmembrane domain. By using antigenic peptides and lipids that were fluorescently...
Article
Full-text available
Infection of H-2 b mice with lymphocytic choriomeningitis virus (LCMV) generates an H-2Db-restricted cytotoxic T-lymphocyte (CTL) response whose subdominant component is directed against the GP92-101 (CSANNSHHYI) epitope. The aim of this study was to identify the functional parameters accounting for this subdominance. We found that the two naturall...
Article
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The mechanisms by which antigenic peptides bearing a glycosylation site may be processed from viral glycoproteins, post-translationally modified, and presented by major histocompatibility complex class I molecules remain poorly understood. With the aim of exploring these processes, we have dissected the structural and functional properties of the M...
Chapter
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1. SUMMARY CD8 + CTL recognize peptides bound to MHC class I molecules. These peptides usually are endogenously produced and 8 to 10 residues long. In contrast to CD4 + cells, MHC class I-restricted T cells cannot be activated by superantigens, because these bind only to MHC class II molecules. Crystallographical studies showed that TCR bind MHC cl...
Article
Binding of a specific peptide(s) from a viral protein to major histocompatibility complex (MHC) class I molecules is a critical step in the activation of CD8(+) cytotoxic T lymphocytes (CTLs). Once activated, CTLs can cause lethal disease in an infected host, for example, by killing virus-containing ependymal and ventricular cells in the central ne...
Article
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This study describes a form of partial agonism for a CD8+ CTL clone, S15, in which perforin-dependent killing and IFN-gamma production were lost but Fas (APO1 or CD95)-dependent cytotoxicity preserved. Cloned S15 CTL are H-2Kd restricted and specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260 (SYI...
Article
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Using H-2Kd-restricted CTL clones, which are specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS(252-260) (SYIPSAEKI) and permit assessment of TCR-ligand interactions by TCR photoaffinity labeling, we have previously identified several peptide derivative variants for which TCR-ligand binding and the effic...