Integrative Biology of Emerging Infectious Diseases (IBEID) / Principal investigators
Institut Cochin U 1016 INSERM, UMR 8104 CNRS, Université Paris Descartes
Immunology Départment, 27 rue Fg St Jacques, 75014 Paris
Research area of the Unit
The group works on antigen presentation by dendritic cells (DC), showing that the housekeeping enzyme TPP2 can replace the proteasome to process an epitope from HIV Nef (Seifert Nat Immunol 2003), that DC can crosspresent HIV antigens from live infected CD4+ T cells (Marañón PNAS 2004)4, that human plasmacytoid DC can cross present1, and that humans, like mice, have a specialized DC population for antigen cross-presentation, the BDCA3+ DC population5.
The group discovered the loss of circulating DC in HIV infection (Grassi AIDS 1999; Pacanowski Blood 2001), and conversely the accumulation of proinflammatory MDC8+ monocytes7, the early impairment of IFN-a productive capacity and the imbalance between IL-12 and IL-23 productions during the primary stage of HIV infection, when a balance between the host immune system and the virus is set6. In comparative and collaborative studies between HIV in patient cohorts and simian models, it has established that plasmacytoid DC specifically home into lymphoid organs during pathogenic infection2,3.
Contribution to the programme
The group studies viral interactions within the cellular and organ environment of the host.
Current anti-viral vaccines rely mostly on cross-presentation by DC, but induce disappointing levels of immunogenicity. To improve immunogenicity, we must identify the compartments of antigen uptake and cross-presentation in different DC populations as a function of antigen forms.
To study the mechanisms of HIV pathogenesis, by defining better and better DC populations, the group found better and better correlations with the stage and prognosis of HIV infection. Now it tackles new DC (BDCA3+) and monocytic (M-DC8+) populations. It studies on how and why compartmentalization is modified by HIV or SIV infections, using clinical samples (spleens, lymph nodes, gut…) and microscopic and flow cytometric cell sorting in L2/L3 facilities. The group seeks the rationale for new immunotherapy protocols, notably to prevent immune hyperactivation while improving antiviral responses.
References (Maximum 7 major publications over the past 5 years)
1. Hoeffel, G., Ripoche, AC., Matheoud, D., Nascimbeni, M., Escriou, N., Lebon, P., Heshmati, F., Guillet, Gannage, M., Caillat-Zucman, S., Casartelli, N., Schwartz, O., De la Salle, H., J.G., Hanau, D., Hosmalin, A. and Marañón, C. Antigen cross-presentation by human Plasmacytoid Dendritic Cells. Immunity, 2007; 27:481-492
2. MalleretB., ManéglierB., KarlssonI., LebonP.,NascimbeniM., PerieL., BrochardP., DelacheB., CalvoJ., AndrieuT., Spreux-VaroquauxO., Hosmalin A., Le GrandR. and VaslinB. Primary infection with simian immunodeficiency virus: Plasmacytoid dendritic cell homing to lymph nodes, type I IFN and immunosuppression, Blood 2008; 112: 4598-4606
3. Nascimbeni, M.*, Perié, L.*, Chorro, L., Diocou, S., Kreitmann, L., Louis, S., Garderet, L., Fabiani, B., Berger, A., Schmitz, J., Marie, J. P., Molina, T. J., Pacanowski, J., Viard, J. P., Oksenhendler, E., Beq, S., Amar, O., Cheynier, R., and Hosmalin, A. Plasmacytoid dendritic cells accumulate in spleens from chronically HIV-infected patients, but barely participate in interferon alpha production. Blood 2009; 113: 6112-6119 * co-first authors
4. Matheoud, D., Perié L., Vimeux, L., Hoeffel, G., Parent, I., Marañón, C, Bourdoncle, P., Renia, L., Blondel, A., Lucas, B., Feuillet *V., Hosmalin *, A. Cross-presentation by dendritic cells from live cells induces protective immune responses in vivo. Blood 2010; 115: 4412-4420 * corresponding authors
5. Crozat, K., Guiton*, R., Contreras*, V., Feuillet*, V., Dutertre*, C. A., Ventre, E., Vu Manh, T. P., Baranek, T., Storset, A. K., Marvel, J., Boudinot, P., Hosmalin#, A., Schwartz-Cornil#, I. and Dalod, M., The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8 a+ dendritic cells. * and # : equal contribution. J Exp Med. 2010; 207: 1283-1292
6. Louis, S.* Dutertre, C.A.*, Fery, L., Henno, L., Vimeux, L., Diocou, S., Kahi, S., Deveau, C., Meyer, L., Goujard, C., and Hosmalin, A. IL-23 and IL-12 p70 production by monocytes and dendritic cells in primary HIV-1 infection. J. Leuko. Biol. 2010; 87: 645-653
7. Dutertre, C.A., Amraoui*, S., DeRosa*, A.L., Jourdain, J.P., Vimeux, L., Goguet, M., Degrelle, S., Feuillet, V., Liovat, A.S., Müller-Trütwin, M., Decroix, N., Deveau, C., Meyer, L., Goujard, C., Loulergue, P., Launay, O., Richard, Y., Hosmalin, A. Pivotal role of M-DC8+ monocytes in the TNFa overproduction of viremic HIV-infected patients. Blood, 2012; 120: 2259-2268