Background: Multiple Sclerosis (MS) is a chronic autoimmune condition associated with demyelination and inflammation within the central nervous system, resulting in neuronal dysfunction and a range of symptoms, including spasticity and cognitive disturbances. MS is histopathologically characterised by inflammatory lesions within the central nervous system (CNS). In Ireland, over 9,000 people are afflicted with MS, and approximately 290 people are diagnosed each year. MS clinical presentation is classified as relapsing remitting (RR), primary progressive (PP) or secondary progressive (SP). MS predominantly affects women aged between 20-40 years old; however, children and older adults can also be afflicted. The innate immune response to bacterial and viral molecules involves the coordinated production of cytokines and chemokines, orchestrated by the innate immune pattern recognition receptors, toll-like receptors (TLRs). Humans possess 10 functional TLRs, which are expressed in immune and CNS cells, where they recognise viral/bacterial molecules. Several human studies have shown that TLR expressions profiled are elevated in MS brain lesions and in immune cells from people with (pwMS). Indeed, host laboratory data has shown that immune cells from pwMS are hypersensitive to TLR activation in terms of cytokine expression. The study hypothesis is that innate immune inflammatory signalling is dysregulated centrally (in the CNS) in response to inflammation in MS. The aim of this project is to use human post-mortem brain samples from the UK MS brain tissue bank, a resource of neuropathologically characterised post-mortem specimens, to assess the expression profiles of TLRs. The objective of this project is to determine expression profiles of TLRs within the CNS using an immunohistochemical approach alongside real-time PCR to determine relative TLR protein and mRNA expression, respectively. Such data will shed light on the pathogenesis of the disorder, simultaneously identifying potential targets for future therapeutics by targeting TLR signalling.
