Domiciliation, activation immunitaire et infection

Bases moléculaires de pathologies humaines

Toutes les équipes de recherche

De plus en plus d’arguments plaident en faveur de l’existence d’un lien causal entre une activation prolongée du système immunitaire et le développement de maladies chroniques comme l’athérosclerose, le syndrome metabolique et le diabète de type 2, la stéatose hépatique, les troubles neurocognitifs, l’ostéoporose, la fragilité et même certains types de cancer.
L’infection par le VIH est un bon modèle pour étudier ces liens. Notre groupe travaille sur l’activation immunitaire chronique, ses causes et ses conséquences, chez les personnes vivant avec le VIH avirémiques sous traitement, appelées répondeurs virologiques. Notre hypothèse de travail est que les répondeurs virologiques pourraient présenter différents profils d’activation immunitaire que nous souhaitons caractériser. Chacun de ces profils d’activation immunitaire pourraient être causé par des facteurs étiologiques propres, comme la persistance d’une production rétrovirale ou d’une lymphopénie T4, une translocation microbienne, des coinfections, une immunosénescence, et/ou une dérégulation de l’équilibre Th17/Treg. Par ailleurs chacun de ces profils immunitaires pourrait favoriser la survenue de comorbidités spécifiques.
En plus de faciliter l’émergence de maladies chroniques, la suractivité du système immunitaire durant des années semble entraver la restauration du pool des cellules T4. Nous étudions comment une forme particulière d’activation monocytaire pourrait être impliquée dans ce phénomène.
Un autre problème pour les répondeurs virologiques est la persistance du génome rétroviral dans ce qu’il est convenu d’appeler des cellules réservoirs. Cette persistance empêche l’éradication du VIH. C’est pourquoi la communauté scientifique est à la recherche de molécules capables de forcer les cellules réservoirs à produire des particules virales dans le but de provoquer leur destruction. A la suite d’un screening systématique des récepteurs couplés aux protéines G (GPCR) coexprimés avec le corécepteur CCR5 dans les cellules T4, nous avons identifié des GPCR présents à la surface de cellules réservoirs dont l’activation déclenche une production virale.

figure 1 en

Figure 1. Virologic responders present with different immune activation profiles. Heatmap showing the hierarchical clustering of the activation markers (vertical) as well as of the virologic responders according to their profile of activation (horizontal). Each Profile number is indicated


Collaborations

  • Division of Hematology, McGill University Health Center, Montréal, Québec, Canada
  • Département des Maladies infectieuses et immunitaires, CHU Laval, Québec, Canada
  • INSERM U1065, Nice, France
  • Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris, France
  • Hôpital Saint-Antoine, Département de Santé Publique, AP-HP, Paris France
  • Université Paris Descartes, Sorbonne Paris Cité; AP-HP, CIC Cochin Pasteur, Hôpital Cochin, Paris, France
  • INSERM, CIC 1417, Paris, F-CRIN, I–REIVAC, France
Pierre CORBEAU
Chercheur
0434359932
Clement METTLING
Chercheur
0434359932
Sandrine Gimenez
Sandrine GIMENEZ
ITA
0434359932

Publications de l'équipe

Angiotensin II induces reactive oxygen species, DNA damage, and T cell apoptosis in severe COVID-19.

Kundura L, Gimenez S, Cezar R, André S, Younas M, Lin YL, Portales P, Lozano C, Boulle C, Reynes J, Thierry V, Mettling C, Pasero P, Muller L, Lefrant JY, Roger C, Claret PG, Duvnjak S, Loubet P, Sotto A, Tran TA, Estaquier J, Corbeau P

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Two-drug vs. three-drug combinations for HIV-1: Do we have enough data to make the switch?

Moreno S, Perno CF, Mallon PW, Behrens G, Corbeau P, Routy JP, Darcis G

Increased Neutrophil Surface PD-L1 Expression in Tobacco Smokers: Consequences for Anti-PD-1 Treatment.

Psomas C, Tuaillon E, Marin G, Reynes J, Corbeau P

Reversing HIV latency via sphingosine-1-phosphate receptor 1 signaling

Duquenne C, Gimenez S, Guigues A, Viala B, Boulouis C, Mettling C, Maurel D, Campos N, Doumazane E, Comps-Agrar L, Tazi J, Prézeau L, Corbeau P, François V.

Plasma Level of Soluble ST2 in Chronically Infected HIV-1 Patients with Suppressed Viremia

Younas M, Psomas C, Mehraj V, Cezar R, Portales P, Tuaillon E, Guigues A, Reynes J, Corbeau P, Routy JP.

Immune activation, smoking, and vaccine response

Younas M, Carrat F, Finge S, Desaint C, Launay O, Corbeau P; ANRS HB03 VIHVAC-B Trial Group

Autophagy-associated dengue vesicles promote viral transmission avoiding antibody neutralization

Wu YW, Mettling C, Wu SR, Yu CY, Perng GC, Lin YS, Lin YL

One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study

Psomas C, Younas M, Reynes C, Cezar R, Portalès P, Tuaillon E, Guigues A, Merle C, Atoui N, Fernandez C, Le Moing V, Barbuat C, Marin G, Nagot N, Sotto A, Eliaou JF, Sabatier R, Reynes J, Corbeau P

Immune activation in the course of HIV-1 infection: Causes, phenotypes and persistence under therapy

Younas M, Psomas C, Reynes J, Corbeau P.

HIV-1 Tat inhibits phagocytosis by preventing the recruitment of Cdc42 to the phagocytic cup

Debaisieux S, Lachambre S, Gross A, Mettling C, Besteiro S, Yezid H, Henaff D, Chopard C, Mesnard JM, Beaumelle B.

The Two Human CXCR4 Isoforms Display Different HIV Receptor Activities: Consequences for the Emergence of X4 Strains

Duquenne C, Psomas C, Gimenez S, Guigues A, Carles MJ, Barbuat C, Lavigne JP, Sotto A, Reynes J, Guglielmi P, Mettling C, François V, Corbeau P

Maraviroc-induced decrease in circulating bacterial products is not linked to an increase in immune activation in HIV-infected individuals.

Psomas C, Lavigne JP, Barbuat C, Trabelsi S, Ghosn J, Lascoux-Combe C, Flandre P, Cuzin L, Reynes J, Autran B, Corbeau P.

+ Méiose et recombinaison

The intensity of immune activation is linked to the level of CCR5 expression in human immunodeficiency virus type 1-infected persons.

Portales P, Psomas KC, Tuaillon E, Mura T, Vendrell JP, Eliaou JF, Reynes J, Corbeau P.

Correction: Combined Phytochemistry and Chemotaxis Assays for Identification and Mechanistic Analysis of Anti-Inflammatory Phytochemicals in Fallopia japonica

Shen MY, Liu YJ, Don MJ, Liu HY, Chen ZW, Mettling C, Corbeau P, Chiang CK, Jang YS, Li TH, Young P, Chang CL, Lin YL, Yang WC

Maraviroc intensification of stable antiviral therapy in HIV-1-infected patients with poor immune restoration: MARIMUNO-ANRS 145 study

Cuzin L, Trabelsi S, Delobel P, Barbuat C, Reynes J, Allavena C, Peytavin G, Ghosn J, Lascoux-Combe C, Psomas C, Corbeau P, Flandre P; the ANRS 145 MARIMUNO Study group.

Combined Phytochemistry and Chemotaxis Assays for Identification and Mechanistic Analysis of Anti-Inflammatory Phytochemicals in Fallopia japonica.

Shen MY, Liu YJ, Don MJ, Liu HY, Chen ZW, Mettling C, Corbeau P, Chiang CK, Jang YS, Li TH, Young P, Chang CL, Lin YL, Yang WC.

Circulating human CD4+ T cells have intracellular pools of CCR5 molecules.

Guglielmi L, Gimenez S, Larroque M, Tong X, Portalès P, Corbeau P.

Immune reconstitution under antiretroviral therapy: a new challenge in HIV-1 infection

Corbeau, P., Reynes, J.

Strategy for anti-aquaporin-4 auto-antibody identification and quantification using a new cell-based assay

De Vidi I, Boursier G, Delouche N, Portalès P, Cadars E, Bouthier M, Mettling C, Lin YL, Thouvenot E, Carlander B, Camu W, Antel JP, Bar-Or A, Zephir H, Vermersch P, De Seze J, Corbeau P, Eliaou JF, Vincent T.

Interleukin-7 induces HIV type 1 R5-to-X4 switch.

Brieu N, Portalès P, Carles MJ, Corbeau P.

Strategy for anti-aquaporin-4 auto-antibody identification and quantification using a new cell-based assay.

De Vidi I, Boursier G, Delouche N, Portalès P, Cadars E, Bouthier M, Mettling C, Lin YL, Thouvenot E, Carlander B, Camu W, Antel JP, Bar-Or A, Zephir H, Vermersch P, De Seze J, Corbeau P, Eliaou JF, Vincent T.

Mesenchymal stem cell-dependent formation of heterotopic tendon-bone insertions (osteotendinous junctions)

Shahab-Osterloh, S., Witte, F., Hoffmann, A., Winkel, A., Laggies, S., Neumann, B., Seiffart, V., Lindenmaier, W., Gruber, AD., Ringe, J., Häupl, T., Thorey, F., Willbold, E., Corbeau, P., Gross, G.

Pairwise Comparison of Isogenic HIV-1 Viruses: R5 Phenotype Replicates More Efficiently Than X4 Phenotype in Primary CD4+ T Cells Expressing Physiological Levels of CXCR4

Fiser AL, Lin YL, Portalès P, Mettling C, Clot J, Corbeau P.

Peripheral blood T4 cell surface CCR5 density as a marker of activity in rheumatoid arthritis treated with anti-CD20 monoclonal antibody.

Portalès P, Fabre S, Vincent T, Desmetz C, Réant B, Noël D, Clot J, Jorgensen C, Corbeau P.

CCR5 antagonism in HIV infection: ways, effects, and side effects

Corbeau, P., Reynes, J.

CXCR3 expression on peripheral CD4(+) T cells as a predictive marker of response to treatment in chronic hepatitis C.

Perney P, Turriere C, Portalès P, Rigole H, Psomas C, Blanc F, Clot J, Corbeau P.

Interfering RNA and HIV: reciprocal interferences

Corbeau P.

Galphai protein-dependant extracellular signal-regulated kinase-1/2 activation is required for HIV-1 reverse transcription

Mettling, C., Desmetz, C., Fiser, AL., Réant, B., Corbeau, P., Lin, YL.

Effective gene therapy in a mouse model of prion diseases

Toupet, K., Compan, V., Crozet, C., Mourton-Gilles, C., Mestre-Francés, N., Ibos, F., Corbeau, P., Verdier, JM., Perrier, V.

The chemokine CCL5 regulates the in vivo cel surface of its receptor, CCR5.

Lin, Y.L., Mettling, C., Portalès, P., Rouzier, R., Clot, J., Reynes, J., Corbeau, P.

Physiological suppression of microRNA-silencing pathway by HIV-1 during virus replication

Triboulet, Robinson., Bernard Mari, Yea-Lih Lin, Christine Chable-Bessia, Yamina Bennasser, Kevin Lebrigand, Bruno Cardinaud, Thomas Maurin, Pascal Barbry, Vincent Baillat, Jacques Reynes, Pierre Corbeau, Kuan-Teh Jeang and Monsef Benkirane.


+ Virologie Moléculaire

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients

Petitjean, G., Al Tabaa, Y., Tuaillon, E., Mettling, C., Baillat, V., Reynes, J., Segondy, M., Vendrell, JP.

Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance

Bakkour, N., Lin, YL., Maire, S., Ayadi, L., Mahuteau-Betzer, F., Nguyen, C.H., Mettling, C., Portales, P. , Grierson, D., Chabot, B., Jeanteur, P., Branlant, C., Corbeau, P., Tazi, J.

Cell surface CCR5 density determines the intensity of T cell migration towards rheumatoid arthritis synoviocytes

Desmetz C, Lin YL, Mettling C, Portales P, Noel D, Clot J, Jorgensen C, Corbeau P.

The strength of the chemotactic response to a CCR5 binding chemokine is determined by the level of cell surface CCR5 density.

Desmetz C, Lin YL, Mettling C, Portales P, Rabesandratana H, Clot J, Corbeau P.

The immunological response to highly active antiretroviral therapy is linked to CD4+ T-cell surface CCR5 density.

Vincent T, Portales P, Baillat V, Eden A, Clot J, Reynes J, Corbeau P.

C-terminal processing of fibrillar procollagens is the only BMP-1-dependent activity to be enhanced by PCPE-1.

Moali, C., Font, B., Ruggiero, F., Eichenberger, D., Rousselle, P., François, V., Oldberg, A., Bruckner-Tuderman, L., Hulmes, D.J.

Structure-based design, synthesis, and biological evaluation of novel inhibitors of human cyclophilin A.

Guichou JF, Viaud J, Mettling C, Subra G, Lin YL, Chavanieu A.

Chordin is under-expressed in ovarian tumors and reduces tumor cells motility.

Moll, F., C. Millet, D. Noël. B. Orsetti, A. Bardin, D. Katsaros, C. Jorgensen, M. Garcia, C. Theillet, P. Pujol and V. François.

The efficiency of R5 HIV-1 infection is determined by CD4 T-cell surface CCR5 density through Galphai-protein signalling.

Lin, YL, Mettling, C., Portales, P., Reant, B., Robert-Hebmann, V., Reynes, J., Clot, J., Corbeau, P.

Prostaglandin D2 induces nuclear import of the sex-determining factor SOX9 via its cAMP-PKA phosphorylation

Malki, S., Nef, S., Notarnicola, C., Thevenet, L., Gasca, S., Méjean, C., Berta, P., Poulat, F., Boizet-Bonhoure, B.


+ Développement et Pathologie de la Gonade

CXCR4 over-expression during the course of HIV-1 infection correlates with the emergence of X4 strains

Lin, Y.-L., Portalès, P., Segondy, M., Baillat, V., Merle de Boever, C., Le Moing, V., Réant, B., Montes, B., Clot, J., Reynes, J., Corbeau, P.

G protein signaling triggered by R5 Human Immunodeficiency Virus type 1 increases virus replication efficiency in primary lymphocytes

Lin, Y.-L., Mettling, C., Portales, P., Réant, B., Clot, J., Corbeau, P.

Effects of virion surface gp120 density on infection by HIV-1 and viral production by infected cells

Bachrach, E., Dreja, H., Lin, Y.-L., Mettling, C., Pinet, V., Corbeau, P., Piechaczyk., M.

T-cell surface CCR5 density is not correlated with hepatitis severity in hepatitis C virus/HIV-coinfected individuals: implications for the therapeutic use of CCR5 antagonists.

Vincent, T., P. Portales, V. Baillat, C. Merle de Boever, V. Le Moing, M. Vidal, J. Ducos, J. Clot, J. Reynes, and P. Corbeau

The expression of cytotoxic mediators is altered in mononuclear cells of patients with melanoma and increased by interferon-alpha treatment.

Guillot, B., Portales, P., Thanh, AD., Merlet, S., Dereure, O., Clot, J., Corbeau, P.

T-cell surface CCR5 density is not correlated with hepatitis severity in hepatitis C virus/HIV-coinfected individuals: implications for the therapeutic use of CCR5 antagonists

Vincent, T., Portales, P., Baillat, V., Merle de Boever, C., Le Moing, V., Vidal, M., Ducos, J., Clot, J., Reynes, J., Corbeau, P.

Vitamin E supplementation increases the expression of the CCR5 coreceptor in HIV-1 infected subjects

Portales, P., Guerrier, T., Mettling, C., Lin, Y.-L., Baillat, V., Merle de Boever, C., Le Moing, V.,Segondy, M., Tramoni, C., Clot, J., Reynes, J., Corbeau, P.

Diminished CD4+ T cell surface CCR5 expression in alcoholic patients

Perney, P., P. Portalès, J. Clot, F. Blanc, and P. Corbeau

Relationship between CCR5 density and viral load after discontinuation of antiretroviral therapy

Reynes, J., Baillat, V., Portalès, P., Clot, J., Corbeau, P.

Feline immunodeficiency virus vectors for efficient transduction of primary human synoviocytes: application to an original model of rheumatoid arthritis

Lin, Y.-L., Noel, D., Mettling, C., Réant, B., Clot, J., Jorgensen, C., Corbeau, P. Reynes J, Baillat V, Portales P, Clot J, Corbeau P.

Deletion of epidermal growth factor-like domains converts mammalian tolloid into a chordinase and effective procollagen C-proteinase

Garrigue-Antar , L., Francois, V., Kadler, K.E.

Low CD4+ T-cell surface CCR5 density as a cause of resistance to in vivo HIV-1 infection

Reynes, J., Baillat, V., Portalès, P., Clot, J., Corbeau, P.

Cholesterol requirement of hepatitis B surface antigen (HBsAg) secretion

Lin, YL., Shiao, MS., Mettling, C. and Chou, CK

Perforin expression in T cells and virological reponse to PEG-interferon alpha2b in HIV-1 infection

Portales, P., Reynes, J., Rouzier-Panis, R., Baillat, V., Clot, J., Corbeau, P

Interferon-alpha restores HIV-induced alteration of natural killer cell perforin expression in vivo

Portales, P., Reynes, J., Pinet, V., Rouzier-Panis, R., Baillat, V., Clot, J., Corbeau, P.

Cell surface CCR5 density determines the postentry efficiency of R5 HIV-1 infection

Lin, Y.-L., Mettling, C., Portales, P., Reynes, J., Clot, J., Corbeau, P.

Response to treatment and disease progression linked to CD4+ T cell surface CC Chemokine Receptor 5 density in Human Immunodeficiency Virus type 1 vertical infection

Gervaix A, Nicolas J, Portales P, Posfay-Barbe K, Wyler CA, Segondy M, Avinens O, Siegrist CA, Clot J, Eliaou JF, Astruc J, Corbeau P

T cell development and T cell responses in mice with mutations affecting tyrosines 292 or 315 of the ZAP-70 protein tyrosine kinase

Magnan A, Di Bartolo V, Mura AM, Boyer C, Richelme M, Lin YL, Roure A, Gillet A, Arrieumeriou C, Acuto O, Malissen B, Malissen M

The human chordin gene encodes several differentially expressed spliced variants with distinct BMP opposing activities.

Millet, C., P. Lemaire, B. Orsetti, P. Guglielmi and V. François

Sex difference in HIV-1 load due to sex difference in CCR5 expression

Portales, P., Clot, J., Corbeau, P.

CD4 T cell surface CCR5 density as a host factor in HIV-1 disease progression

Reynes, J., Portales, P., Segondy, M., Baillat, V., André, P., Avinens, O., Picot, M.-C., Clot, J., Eliaou, J.-F., Corbeau, P.

Rap1 Suppressed Tumorigenesis Is Concomitant with the Interference in Ras Effector Signaling

Lin, Y-L., Mettling, C., Chou, C-K.

Complexes Formation between Insulin Receptor and Extracellular Signal-Regulated Kinase ERKs

Yea-Lih Lin, Clément Mettling and Chen-Kung Chou

CD4+ T cell surface CCR5 density as a determining factor of virus load in persons infected with human immunodeficiency virus type 1

Reynes, J., Portales, P., Segondy, M., Baillat, V., André, P., Réant, B., Avinens, O., Couderc, G., Benkirane, M., Clot, J., Eliaou, J.F., Corbeau, P.

CD4+ T cell surface CCR5 density and virus load in persons infected with Human Immunodeficiency Virus type 1

Reynes, J., Portales, P., Clot, J., Corbeau, P.

Acetylation of the HIV-1 tat protein by p300 is important for its transcriptional activity.

Ott, M., Schnolzer, M., Garnica, J., Fischle, W., Emiliani, S., Rackwitz, H-R., Verdin, E.

Genomic organization and chromosomal localization of the human histone deacetylase 3 gene.

Mahlknecht, U., Emiliani, S., Najfeld, V., Young, S. and Verdin, E.

A new family of histone deacetylases related to Saccharomyces Cerevisae HDA1p.

Fischle, W., Emiliani, S., Hendzel, M.J., Nagase, T., Nomura, N., Voelter, W. and Verdin, E.

Phosphatidylinositol 3-Kinase Is Required for the Regulation of Hepatitis B Surface Antigen Production and Mitogen-Activated Protein Kinase Activation by Insulin but Not by TPA

Yea-Lih Lin and Chen-Kung Chou

Hybrid polard compounds selected as inducers of differentiation of transformed cells inhibit histone deacetylase activity.

Richon, V.M., Emiliani, S., Verdin, E., Ngo, L., Webb, Y., Breslow, R., Rifking, R.A. and Marks, P.A.

Characterization of a new human RPD3 ortholog HDAC3.

Emiliani, S., Fischle, W., Van Lint, C., Al-Abed, Y. and Verdin, E.

Mutations in the tat gene are responsible for human immunodeficiency virus type 1 postintegration latency in the U1 cell line.

Emiliani, S., Fischle, W., Ott, M., Van Lint, C., Amella, C.A. and Verdin, E.

Transduction of human macrophages using a stable HIV-1/HIV-2-derived gene delivery system.

Corbeau, P., Kraus, G. and Wong-Staal, F.

Anti-HIV effects of HIV vectors.

Corbeau, P. and Wong-Staal, F.

Thèses et hdr

Sujet: Infections par SARS-COV-2 et par VIH-1 : activations immunitaires aigüe et chronique 03/11/2021

Soutenue par Lucy Kundura le 03/11/2021

Interactions entre CCR5 et trois récepteurs couplés aux protéines G : EBI2, A2A et S1P1 : effets sur l'infection par le VIH-1, mécanismes d'action et perspectives thérapeutiques 16/11/2017

Soutenue par Adeline Guigues sous la direction de Pierre Corbeau et de Vincent François à Montpellier le 16/11/2017

Responsable : Pierre CORBEAU


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financeurs

Université de Montpellier Sidaction MSD Avenir Gilead Sciences CHU Nîmes CHU Montpellier Agence nationale de recherches sur le Sida et les hépatites virales