M2 Research Internship

Host Team: Laboratory of Immunity and Transmission
Unit Name: Center for Immunology of Viral, Autoimmune, Hematological and Bacterial
Diseases (ImVA-HB), CEA/DRF/Université Paris Saclay/JACOB/IDMIT/INSERM U1184
Website: IDMIT Center (http://www.idmitcenter.fr)
Unit Head: Roger Le Grand
Adress: 18 route du Panorama, 92265 Fontenay-aux-Roses
Supervisor: Mariangela Cavarelli
E-mail: mariangela.cavarelli@cea.fr

Harnessing Gut-Derived Postbiotics to Boost Immune Responses to

Project Summary:
HIV-1 remains a formidable challenge despite extensive research efforts. Antiretroviral therapy (ART) effectively blocks active infection but struggles to target latent proviruses, a major hurdle in achieving a cure. There is compelling evidence that CD8+ T cells play a central role in both natural and ART-induced HIV-1 control. This opens up promising avenues for remission, cure, and vaccine strategies.
Our research focuses on a critical viral immune evasion strategy—downregulation of human leukocyte antigen (HLA) class I molecules on HIV-infected CD4+ T cells, which prevents their recognition by HIV-specific CD8+ T cells. Additionally, the breakdown of the gastrointestinal mucosal barrier exacerbates immune activation and contributes to CD8+ T cell exhaustion.
Our project leverages the unique role of the gut microbiota in influencing disease outcomes. The gut microbiota, physically separated from intestinal epithelial cells by mucus, exerts its beneficial effects through bacteria-derived metabolites. Using innovative in vitro and ex vivo models of infection, we aim to explore the multifaceted potential of gut-derived postbiotics. Our focus is on their impact on CD8+ T cell responses and the preservation of intestinal epithelial barrier integrity.
The insights gained from this study promise to contribute significantly to innovative HIV treatment and prevention strategies.
We are seeking a motivated student willing to continue with a thesis.

Application Requirements:
• CV
• Motivation letter
• Transcripts from M1 and M2 courses and exams
• Contact information of one reference
Please send your complete application (one pdf) to mariangela.cavarelli@cea.fr
Join us and take the first step toward a rewarding research career!

Related recent publications from the group:
1. S. Hua, K. Latha, R. Marlin, K. Benmeziane, L. Bossevot, S. Langlois, F. Relouzat, N. Dereuddre-Bosquet, R. Le Grand, M. Cavarelli. Intestinal immunological events of acute and resolved SARS-CoV-2 infection in non-human primates. Mucosal Immunology. October 2023. https://doi.org/10.1016/j.mucimm.2023.10.001
2. K. Suphaphiphat, D. Desjardins, V. Lorin, N. Dimant, K. Bouchemal, L. Bossevot, M.Galpin-Lebreau, N. Dereuddre-Bosquet, H. Mouquet, R. Le Grand, M. Cavarelli. Mucosal application of the broadly neutralizing antibody 10-1074 protects
macaques from cell-associated SHIV vaginal exposure. Nature Communications, October 2023. https://doi.org/10.1038/s41467-023-41966-4
3. M. Van Tilbeurgh, P. Maisonasse, J.L.Palgen, M. Tolazzi, Y. Aldon, N. Dereuddre- Bosquet, M. Cavarelli, A.S. Beignon, E. Marcos-Lopez, A.S. Gallouet, E. Gilson, G. Ozorowski, A.B. Ward, I. Bontjer, P.F. McKay, R. J. Shattock, G. Scarlatti, R. W. Sanders, R. Le Grand. Innate cell markers that predict anti-HIV neutralizing antibody titers in vaccinated macaques. Cell Report Medicine. 2022. DOI:https://doi.org/10.1016/j.xcrm.2022.100751
4. M Cavarelli, C Foglieni, N Hantour, T Schorn, A Ferrazzano, S Dispinseri, D Desjardins, U Elmore, N Dereuddre-Bosquet, G Scarlatti, R Le Grand. Identification of CX3CR1+ mononuclear phagocyte subsets involved in HIV-1 and SIV colorectal transmission. iScience 2022. doi: https://doi.org/10.1016/j.isci.2022.104346.
5. M Cavarelli, S Hua, N Hantour, S Tricot, N Tchitchek, C Gommet, H Hocini, C Chapon, N Dereuddre-Bosquet, R Le Grand. Leukocytospermia induces intraepithelial recruitment of dendritic cells and increases SIV replication in colorectal tissue explants. Communications Biology 2021, 4:861. doi: 10.1038/s42003-021-02383-9
6. R Marlin, V Godot, S Cardinaud, M Galhaut, S Coleon, S Zurawski, N Dereuddre-Bosquet, M Cavarelli, AS Gallouët, … S van der Werf, G Pantaleo, R Thiébaut, G Zurawski, Y Lévy, and R Le Grand. Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques. Nature Communications. 2021Sep 1;12(1):5215. 10.1038/s41467-021-25382-0