Project's members
Project
Dendritic cells (DCs) play a crucial role in antiviral responses, particularly through their specialization in antigen processing and presentation to T lymphocytes, as well as through their production of interferons (IFNs) with strong antiviral activity. Plasmacytoid dendritic cells (pDCs) are the main producers of interferon-alpha (IFN-α), and they also produce interferon-lambda (IFN-λ), which plays a specific role in epithelial defenses due to its receptor being non-ubiquitously expressed, unlike IFN-α.
By showing that CD11c+ DCs (conventional DCs) were reduced in number during HIV infection, we were the first to study DC counts in a pathological context. We subsequently found that pDCs are also reduced in number and that their IFN production function is impaired from the early phase of infection. Over the course of the infection, pDCs relocate to secondary lymphoid organs. In contrast to DCs, slan-monocytes—which are highly pro-inflammatory—are increased in the circulation of viremic people living with HIV.
CD8 T cell responses help control HIV infection. We were the first to demonstrate that the main human blood DC subsets are all capable of cross-presenting HIV antigens to CD8 T lymphocytes. A unique aspect of our research is the demonstration that this cross-presentation can occur not only from dead cells but also from live cells. After an initial in vitro demonstration using human DCs, we showed that this discovery is relevant in vivo for immune defense in a murine melanoma model.
We are currently investigating the potential heterogeneity of pDCs regarding their various roles in HIV defense: production of IFN-α and IFN-λ, antigen presentation to T lymphocytes, and—in collaboration with Fatah Ouaaz, Florence Niedergang, and other team members—antigen capture and presentation to B lymphocytes.
We are also studying the differences in their responses to HIV-2 compared to HIV-1, both in vitro and in patients enrolled in the Immunovir study, a sub-study of the ANRS CO-5 cohort, in collaboration with the coordinators of that cohort.
References
- Isnard*, S., Hatton*, E.X., Iannetta, M., Guillerme, J-B. and Hosmalin A. Cell-associated HIV cross-presentation by pDC is potentiated by non-cognate CD8+ T cell preactivation, J. Immunol. 2021, 207: 15-22. doi: 10.4049/jimmunol.2000392.
- Isnard, S., E. Hatton, E.X., Guillerme, and A. Hosmalin. Monitoring antigen cross-presentation with human dendritic cells purified from the blood. Tumor Immunology and Immunotherapy - Integrated Methods, Lorenzo Galluzzi, L. and Nils-Petter Rudqvist, N.P., eds. Methods in Enzymology, Elsevier, 2020;635:283-305. doi: 10.1016/bs.mie.2020.01.004. Epub 2020 Feb 11.
- Segura, E, Touzot M, Bohineust A, Cappuccio A, Chiocchia G, Hosmalin A, Dalod M, Soumelis V, and Amigorena S. Human Inflammatory Dendritic Cells Induce Th17 Cell Differentiation. Immunity, 2013; 38: 336-48
- Matheoud, D., Baey, C., Vimeux, L., Tempez, A., Valente, M., Louche, P., Le Bon, A., Hosmalin*, A., Feuillet*, V. Dendritic cells crosspresent antigens from live B16 cells more efficiently than from apoptotic cells and protect from melanoma in a therapeutic model. PLOS One 2011 ;6(4):e19104.
- 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. ⟨10.1182/blood-2009-11-255935⟩. ⟨hal-00493469⟩* : corresponding authors
- 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. ⟨10.1084/jem.20100223⟩. ⟨hal-00493468⟩
- Hoeffel, G., Ripoche, AC., Matheoud, D., Nascimbeni, M., Escriou, N., Lebon, P., Heshmati, F., Guillet, J.G., Gannage, M., Caillat-Zucman, S., Casartelli, N., Schwartz, O., De la Salle, H. Hanau, D., Hosmalin, A. and Marañón, C. Antigen cross-presentation by human Plasmacytoid Dendritic Cells. Immunity, 2007 ; 27 :481-492
- Marañón, C., Desoutter, J. F., Hoeffel, G., Cohen, W., Hanau, D., and Hosmalin, A. Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes. Proc. Natl. Acad. Sci. USA, 2004;101:6092-6097.
- Seifert, U., Marañón, C., Shmueli A., Desoutter, J.F., Wesoloski, L., Janek, K., Henklein, P., Diescher, S., K., Andrieu, M., de la Salle, H., Weinschenk, T., Schild, H., Laderach, D., Galy, A., Haas, G., Kloetzel, P.M., Reiss, Y. and Hosmalin, A. An essential role for TPPII in the generation of an MHC class I epitope. Nature Immunol, 2003; 4:375-379.
