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Suppression of adaptive immunity by Salmonella (360G-Wellcome-209411_Z_17_Z)

Dendritic cells (DCs) have a crucial role in the development of adaptive immunity to bacteria. DCs transport the intracellular pathogen Salmonella from intestinal Peyer’s Patches to mesenteric lymph nodes where they present bacterial antigens to CD4+ T cells using MHCII molecules. DCs also secrete cytokines that stimulate recruitment and activation of T and NK cells. Salmonella is a globally important intracellular pathogen that survives in DCs and interferes with the processes of DC migration, cytokine production/sensing and T cell activation. The overall goal of this application is to understand mechanisms by which Salmonella interferes with these processes. Recently we identified an effector of the SPI-2 type III secretion system (SteD) that reduces the number of mature MHCII molecules on the surface of DCs. A significant component of the planned work is to understand its mechanism of action in detail. We will use candidate-based and unbiased screens, along with molecular cell biological approaches to characterize mechanisms involved in suppressing DC migration, production of IL-12 and IFN-gamma-stimulated host cell signaling. Collectively, this research will advance the field by providing novel insights into different mechanisms by which a bacterial pathogen subverts the development of adaptive immunity.

£2,170,670

28 Nov 2017

Grant details
Amount Awarded 2170670
Applicant Surname Holden
Approval Committee Science Interview Panel
Award Date 2017-11-28T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Investigator Award in Science
Internal ID 209411/Z/17/Z
Lead Applicant Prof David Holden
Planned Dates: End Date 2023-09-01T00:00:00+00:00
Planned Dates: Start Date 2018-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
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