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SENTINEL SIGNED

HIV-1 sensing and signaling in dendritic cells

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

SENTINEL project word cloud

Explore the words cloud of the SENTINEL project. It provides you a very rough idea of what is the project "SENTINEL" about.

human suggests insensitive dysfunction feasibility elucidating vivo underscore therapy models suppression suppresses mechanism oncogenes sentinel innovation chronic million strikingly enhanced cancer health innate machinery delays drugs mechanisms screen induction counteracting antagonizing suffer proto cells hypothesize global paradigm morbidities clinically dendritic survival polymorphism suggest immune cohort infections severe data infected underlies progression antiviral ex evades establishment expertise immunity co strategies restore limit gene anti shape amsterdam delayed sensing hiv disease therapies cell improves infection approved paramount patients antiretroviral rendering tissue group innovative actively

Project "SENTINEL" data sheet

The following table provides information about the project.

Coordinator	ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM Organization address address: MEIBERGDREEF 15 city: AMSTERDAM postcode: 1105AZ website: www.amc.nl contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
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.

#	participants	country	role	EC contrib. [€]
1	ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM Organization address address: MEIBERGDREEF 15 city: AMSTERDAM postcode: 1105AZ website: www.amc.nl contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	NL (AMSTERDAM)	coordinator	2˙499˙156.00

Map

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

List of 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-Iâ€“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 TRIM5Î± 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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The information about "SENTINEL" are provided by the European Opendata Portal: CORDIS opendata.