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    Team: Cytokines and Viral Infections

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    Team leader 

    (CV)

     

    Cytokines, essential proteins for the immune system, are secreted by T- and B-lymphocytes, macrophages and dendritic cells but also by various cell types that do not belong to the immune system. These factors allow maintaining the homeostatic equilibrium of the immune system and modulate immune responses. Our team explores cytokine productions in the mucosae of primates during acute infections as well as their role in the development of anti-viral immune responses.

     

    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 firstly aim to identify the physiopathological mechanisms.

    Our projects aim firstly to highlight the pathophysiological mechanisms during this phase of infection and, secondly, to identify molecules capable of specifically stimulating 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 a new fuction of IL-7 that address immune cells to the mucosa. We also explore the involvement of type I interferon (IFN), a major cytokine 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 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 the 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.

     

     

    Main publications

     

    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.

    Rancez M., Couëdel-Courteille A. and Cheynier R. (2012). Chemokines at mucosal barriers, impact on HIV infection. Cytokine & Growth Factor Reviews. 23(4-5):233-43.

    Jacobelli S., Sanaa F., Moyal-Barracco M., Pelisse M., Berville S., Villefroy P., North M-O., Figueiredo S., Charmeteau B., Clerici T., Plantier F., Arnold F., Touzé A., Dupin N., Avril M-F., Guillet J-G., Cheynier R. and Bourgault-Villada I. (2012) Anti-HPV16 E2 protein T-cell responses and viral control in women with usual vulvar intraepithelial neoplasia and their healthy partners. PloS One. 7(5): e37042.

    Fabre-Mersseman V., Dutrieux J., Louise A., Rozlan S., Lamine A., Parker R., Rancez M., Nunes-Cabaço H., Sousa AE., Lambotte O. and Cheynier R. (2011) CD4+ recent thymic emigrants are infected by HIV in vivo, implication for pathogenesis. AIDS. Jun 1;25(9):1153-1162.

    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.

     

     

    Team news

     

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