Tuft Cell Activation and Intestinal Immunity (360G-Wellcome-211814_Z_18_Z)
Immunity to nematode parasites requires sequential activation of innate and adaptive immunity in a concerted Type 2 response dependent on the cytokines IL-4, IL-13 and IL-25. Our work, and that of others, has identified a novel epithelial cell type that is critical to initiation of this response, known as tuft (or brush) cells. Most significantly, tuft cells are a major source of IL-25 during gastro-intestinal nematode infection, which induces IL-13 production from innate lymphoid cell type 2 (ILC2s), to activate further innate and adaptive cell populations. They also express high levels of the enzymes that produce acetylcholine and lipid mediators implicated in immunity. Tuft cells are found in other mucosal locations, including the lungs, and are highly conserved across the Mammalia, including in ruminants where intestinal nematodes are a major problem. A fascinating aspect is their expression of taste receptors suggesting that they may chemically ‘sense’ the presence of nematodes. In this proposal we seek to (i) determine the immune effector functions of tuft cell mediators; (ii) identify molecules from parasites that may activate tuft cells; and (iii) establish whether tuft cell functions are conserved in ruminants and may lead to new strategies for control of nematode infection in sheep.
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Grant Details
Amount Awarded | 1203739 |
Applicant Surname | Maizels |
Approval Committee | Science Interview Panel |
Award Date | 2018-07-17T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Collaborative Award in Science |
Internal ID | 211814/Z/18/Z |
Lead Applicant | Prof Richard Maizels |
Other Applicant(s) | Dr Collette Britton, Dr Philippe Jay, Dr Tom McNeilly, Prof Eileen Devaney |
Partnership Value | 1203739 |
Planned Dates: End Date | 2023-11-05T00:00:00+00:00 |
Planned Dates: Start Date | 2018-11-05T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Scotland |