Contrasting immune adaptation in peripheral organs and the central nervous system in response to chronic infection in health and disease. (360G-Wellcome-082057_Z_07_Z)

£327,553

Systemic inflammation or infection leads to the generation of inflammatory cytokines in the periphery that communicate with the brain to initiate cytokine synthesis there. These cytokines in the brain in turn give rise to fever and behavioural changes such as anorexia, loss of activity and depression, known as sickness behaviour. It is well known that repeated or sustained systemic inflammatory challenges lead to a state of immune tolerance in the periphery: an important protective mechanism ag ainst over-activity of the immune system. We will investigate whether there is a state of immune tolerance induced in the brain, after repeated or sustained peripheral inflammatory challenges, using measures of cytokine production and the associated behaviours. We have evidence that, in brain, repeated systemic challenges do not lead to the same state of innate immune tolerance as seen in the periphery. We will investigate the cell types and potential pathways involved in the non-tolerant state. We will investigate whether an immune tolerant state is evoked in brains with ongoing neurodegeneration, in which the innate immune system is already primed by the pathology. We predict that the lack of innate immune tolerance mechanisms in the brain will exacerbate the progression of chronic neurodegenerative disease.

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Grant Details

Amount Awarded 327553
Applicant Surname Perry
Approval Committee Molecular and Cellular Neuroscience Funding Committee
Award Date 2007-05-03T00:00:00+00:00
Financial Year 2006/07
Grant Programme: Title Project Grant
Internal ID 082057/Z/07/Z
Lead Applicant Prof Victor Perry
Other Applicant(s) Prof Jessica Teeling
Partnership Value 327553
Planned Dates: End Date 2010-11-30T00:00:00+00:00
Planned Dates: Start Date 2007-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East