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    Team: Cytokines and Viral Infections


    Team leader 



    Cytokines, essential proteins for the functioning of the immune system, are secreted by T- and B- lymphocytes, macrophages, dendritic cells, but also by cells that do not belong to the immune system. These factors allow maintaining the homeostatic equilibrium of the immune system and modulate the immune responses. Our team explores the production of cytokines in tissues during acute viral infections and their involvement in the development of antiviral immune responses, mainly in mucosae. These projects are carried out in different experimental models both in vitro and in vivo (simians and more recently murine), as well as in humans. Finally, we are particularly interested in IL7, a cytokine for which we have demonstrated a new role in the targeting of immune cells to mucous membranes. We seek to understand its mechanisms of action and explore the use of this cytokine as a mucosal vaccine adjuvant in different infectious models.


    Objectives :

    Our team explores the role of cytokines and chemokines locally produced as a consequence of mucosal viral infections in several natural and experimental models of acute infections, in both humans and animal models. Our projects aim at identifying the physiopathological mechanisms implicated during this phase of infection and at defining molecules capable of specifically stimulate mucosal immune responses. We explore more particularly the functions of IL-7, an essential cytokine regulating the homeostasis of the immune system. Indeed, we evidenced the implication of IL-7 in immune cells addressing to mucosae. We also explore the involvement of type I interferons (IFN), major cytokines implicated in antiviral response, in the establishment of immunodeficiency triggered by AIDS viruses.

    Through our projects, we seek to understand how IL-7 induces the migration of these cells to and within mucosae and to use this function to stimulate local immunity in mucosal immunization protocols. In collaboration with the Cytheris SA, we explored the impact of IL-7 injections in HIV infected patients. We are also exploring the production of different IFN-α subtypes in the organs of SIV-infected monkey to better understand their impact on viral control during the acute phase of SIV infection and the pathophysiological consequences of these expressions in tissues. Finally, we study the importance of cellular immune responses in the control of oncogenic HPV infection  in patients with vulvar and anal HPV-induced lesions.


    Our team is also involved in many collaborative projects with both French and foreign teams. So, we are providing the community with our expertise in quantifying thymic function in humans. We explored the importance of this function in patients after transplantation of hematopoietic stem cells, bone marrow or thymus, in children thymectomized, presenting chronic granulomatous disease or congenital immunodeficiency (FOXN1-deficiency, DiGeorge syndrome) and in HIV-1 or HIV- 2 infected patients.


    Main publications

    Logerot S, Rancez M, Charmeteau-de Muylder B, Figueiredo-Morgado S, Rozlan S, Tambussi G, Beq S, Couëdel-Courteille A, Cheynier R. HIV reservoir dynamics in HAART-treated poor immunological responder patients under IL-7 therapy. AIDS. 2018 Jan 23. 

    Ponte, R., M. Rancez, S. Figueiredo-Morgado, J. Dutrieux, V. Fabre-Mersseman, B. Charmeteau-de-Muylder, T. Guilbert, J.P. Routy, R. Cheynier and A. Couedel-Courteille, Acute Simian Immunodeficiency Virus Infection Triggers Early and Transient Interleukin-7 Production in the Gut, Leading to Enhanced Local Chemokine Expression and Intestinal Immune Cell Homing. Front Immunol, 2017. 8: p. 588.

    Ponte, R., V. Mehraj, P. Ghali, A. Couedel-Courteille, R. Cheynier and J.P. Routy, Reversing Gut Damage in HIV Infection: Using Non-Human Primate Models to Instruct Clinical Research. EBioMedicine, 2016. 4: p. 40-9.

    Dutertre, C.A., J.P. Jourdain, M. Rancez, S. Amraoui, E. Fossum, B. Bogen, C. Sanchez, A. Couedel-Courteille, Y. Richard, M. Dalod, V. Feuillet, R. Cheynier and A. Hosmalin, TLR3-responsive, XCR1+, CD141(BDCA-3)+/CD8alpha+-equivalent dendritic cells uncovered in healthy and simian immunodeficiency virus-infected rhesus macaques. J Immunol, 2014. 192(10): p. 4697-708.

    Dutrieux J., Fabre-Mersseman V., Charmeteau-De Muylder B., Rancez M., Ponte R., Rozlan S., Figueiredo-Morgado S., Bernard A., Beq S., Couëdel-Courteille A. and CheynierR. (2014) Modified interferon-a subtypes production and chemokine networks in the thymus during acute simian immunodeficiency virus infection, impact on thymopoiesis. AIDS. 28(8):1101-13.

    Beq S., Rozlan S., Gautier D., Parker R., Mersseman V., Schilte C., Assouline B., Rancé I., Lavedan P., Morre M. and Cheynier R. (2009) Injection of Glycosylated Recombinant Simian IL-7 Provokes Rapid and Massive T-cell Homing in Rhesus Macaques. Blood, 114 :816-825.



    French Patent n° 97.15246. Micelles mixtes de lipopeptides pour l’induction d’une réponse immunitaire et leurs utilisations à des fins thérapeutiques. Gras-Masse H, Guillet J.G, Bourgault-Villada I, Bossus M, Lippens G, Wieruszeski, J, Tartar A. License developed by PIL/Biovector.

    International patent WO 02/090382 A2. Mélange de peptides issus des protéines E6 et/ou E7 de papillomavirus et leurs applications. Maillère B, Bourgault Villada I, Pouvelle Morratille S, Guillet J.G. license development (2004-2006) by ISA-PHARMA.

    International patent WO 00/75336 A2. Fragments protéiques polyépitopiques des protéines E6 et E7 de HPV, leur obtention et leurs utilisations, notamment en vaccination. Choppin J, Bourgault Villada I, Guillet J.G, Connan F, Ferries E. Licensed to ISA-PHARMA

    French patent n° FR 0203189. Utilisation de mélange de lipopeptides pour la fabrication de vaccins Guillet J.G, Bourgault Villada I, Dupuis M, Gras Masse H, Bourel L, Melnyk O, Joly P, Bonnet D, Malingue F, Grand Jean C, Georges B.

    US patent application No. 09/607,908 Method for measuring de novo T-cell production in humans

    International patent application No. PCT/CA 02/01839. DNA construct for assessing thymic function activity and therapeutical uses thereof.

    US patent application No.US60/671,483. Molecular tools to evaluate the extent of intrathymic precursor T cell proliferation.


    Team news

    Rémi Cheynier is principal Investigator of a collaborative ANRS project aimed at identifying immune correlates of lower pathogenicity in HIV-2 infection (Immunovir-2).

    Magali Rancez was recruited as CR CNRS in 2014.

    Magali Mas, MCU Paris Descartes joint the team in January 2017.

    The team is part of an international ANR project (ANR-PCRI) that aims at understanding the immune mechanisms leading to protection induced by yellow fever vaccine. This project will be performed in collaboration with Giovanna Barba-Spaeth (Institut Pasteur-Paris), Simon Rothenfusser (Ludwig-Maximilians-Universität München) and Anne Krug (Ludwig-Maximilians-Universität München).

    Anne Couëdel-Courteille participated to the race: La course du souffle "Les virades de l'espoir pour vaincre la mucoviscidose" in September 2017.