SENTINEL SIGNED
HIV-1 sensing and signaling in dendritic cells
Total Cost €
0EC-Contrib. €
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Explore the words cloud of the SENTINEL project. It provides you a very rough idea of what is the project "SENTINEL" about.
Project "SENTINEL" data sheet
The following table provides information about the project.
| Coordinator |
ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Organization address contact info |
| Coordinator Country | Netherlands [NL] |
| Total cost | 2˙499˙156 € |
| EC max contribution | 2˙499˙156 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-ADG |
| Funding Scheme | ERC-ADG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-10-01 to 2020-09-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM | NL (AMSTERDAM) | coordinator | 2˙499˙156.00 |
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Project objective
HIV-1 is a major global health problem with over 2 million new infections every year, and although antiretroviral therapy is effective, chronic infected patients suffer from severe co-morbidities due to immune dysfunction. With the proposed SENTINEL project, I aim to identify novel strategies to enhance innate antiviral immunity to HIV-1 to limit establishment and progression of chronic disease. Our novel data strongly suggest that induction of antiviral innate immune responses in dendritic cell subsets delays disease progression and improves survival in chronic HIV-1-infected patients. Current paradigm suggests that HIV-1 evades innate sensing in dendritic cells and that this underlies immune dysfunction. However, our innovative data demonstrate that HIV-1 actively suppresses a novel innate sensing mechanism and antagonizing this HIV-1 suppression by drugs strongly enhanced antiviral immunity. Strikingly, we identified a gene polymorphism in a component of the novel HIV-1 sensing machinery, rendering the pathway insensitive to HIV-1 suppression; this polymorphism is associated with delayed disease progression and improved survival in HIV-1 patients from the Amsterdam Cohort Studies. Thus, I hypothesize that therapies counteracting the suppression by HIV-1 will enhance antiviral immunity and restore immune dysfunction in chronic patients. Within this SENTINEL project, novel targets for HIV-1 therapy will be identified. As we identified proto-oncogenes involved in the suppression of innate immune responses by HIV-1, we will also screen clinically approved anti-cancer drugs as novel therapies to enhance the innate immune responses to HIV-1. Our exciting data strongly underscore the innovation and feasibility of the project. The unique expertise of my group in elucidating complex mechanisms that shape immunity, our innovative ex vivo human tissue infection models and cohort studies will be crucial in the proposed research and paramount to its success.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2017 |
Joris K. Sprokholt, Marieke H. Heineke, Tanja M. Kaptein, John L. van Hamme, Teunis B. H. Geijtenbeek DCs facilitate B cell responses against microbial DNA via DC-SIGN published pages: e0185580, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0185580 |
PLOS ONE 12/10 | 2019-09-02 |
| 2017 |
Joris K. Sprokholt, Tanja M. Kaptein, John L. van Hamme, Ronald J. Overmars, Sonja I. Gringhuis, Teunis B. H. Geijtenbeek RIG-I–like Receptor Triggering by Dengue Virus Drives Dendritic Cell Immune Activation and T H 1 Differentiation published pages: 4764-4771, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1602121 |
The Journal of Immunology 198/12 | 2019-09-02 |
| 2017 |
Nina Hertoghs, Teunis B.H. Geijtenbeek, Carla M.S. Ribeiro Interplay between HIV-1 innate sensing and restriction in mucosal dendritic cells: balancing defense and viral transmission published pages: 112-119, ISSN: 1879-6257, DOI: 10.1016/j.coviro.2017.01.001 |
Current Opinion in Virology 22 | 2019-09-02 |
| 2017 |
Joris K. Sprokholt, Tanja M. Kaptein, John L. van Hamme, Ronald J. Overmars, Sonja I. Gringhuis, Teunis B. H. Geijtenbeek RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production published pages: e1006738, ISSN: 1553-7374, DOI: 10.1371/journal.ppat.1006738 |
PLOS Pathogens 13/11 | 2019-09-02 |
| 2016 |
Teunis B. H. Geijtenbeek, Sonja I. Gringhuis C-type lectin receptors in the control of T helper cell differentiation published pages: 433-448, ISSN: 1474-1733, DOI: 10.1038/nri.2016.55 |
Nature Reviews Immunology 16/7 | 2019-09-02 |
| 2018 |
Marta Bermejo-Jambrina, Julia Eder, Leanne C. Helgers, Nina Hertoghs, Bernadien M. Nijmeijer, Melissa Stunnenberg, Teunis B. H. Geijtenbeek C-Type Lectin Receptors in Antiviral Immunity and Viral Escape published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.00590 |
Frontiers in Immunology 9 | 2019-09-02 |
| 2016 |
Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani, Joris K Sprokholt, Nienke H van Teijlingen, Neeltje A Kootstra, Thijs Booiman, Karel A van Dort, Carla M S Ribeiro, Agata Drewniak, Teunis B H Geijtenbeek HIV-1 blocks the signaling adaptor MAVS to evade antiviral host defense after sensing of abortive HIV-1 RNA by the host helicase DDX3 published pages: 225-235, ISSN: 1529-2908, DOI: 10.1038/ni.3647 |
Nature Immunology 18/2 | 2019-09-02 |
| 2018 |
Melissa Stunnenberg, Teunis B.H. Geijtenbeek, Sonja I. Gringhuis DDX3 in HIV-1 infection and sensing: A paradox published pages: 32-39, ISSN: 1359-6101, DOI: 10.1016/j.cytogfr.2018.03.001 |
Cytokine & Growth Factor Reviews 40 | 2019-09-02 |
| 2016 |
Carla M. S. Ribeiro, Ramin Sarrami-Forooshani, Laurentia C. Setiawan, Esther M. Zijlstra-Willems, John L. van Hamme, Wikky Tigchelaar, Nicole N. van der Wel, Neeltje A. Kootstra, Sonja I. Gringhuis, Teunis B. H. Geijtenbeek Receptor usage dictates HIV-1 restriction by human TRIM5α in dendritic cell subsets published pages: 448-452, ISSN: 0028-0836, DOI: 10.1038/nature20567 |
Nature 540/7633 | 2019-09-02 |
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