Prof. Sandra SACRE
Brighton and Sussex Medical School
University of Sussex
Brighton, ENGLAND
Website

Program

"Insights into toll-like receptor and NLRP3 inflammasome activation in chronic inflammatory disease"

The innate immune system is the first line of defence against pathogens. Pattern recognition receptors such as toll-like receptors (TLRs) initiate inflammatory signalling pathways in response to pathogen-associated molecular patterns. Upon activation, TLRs produce proinflammatory cytokines including tumour necrosis factor, interleukin (IL)-1-beta and IL-6. However, IL-1-beta additionally requires formation of an inflammasome to cleave pro-IL-1-beta to the active form and to truncate gasdermin D, releasing the N-terminal domain, which forms pores within the membrane enabling IL-1-beta release. Inflammasomes are cytoplasmic multiprotein complexes that are key sensors of cellular stress, of which the NLRP3 inflammasome is the most widely studied.

In addition to pathogen recognition, TLRs also function as sensors of cellular damage, responding to endogenous molecules released at sites of inflammation and tissue damage. Consequently, TLRs and the NLRP3 inflammasome are associated with the pathogenesis of many chronic sterile inflammatory diseases, where they contribute to the perpetuation of inflammation. This presentation will provide an overview of TLR and NLRP3 inflammasome activation in primary human cells and will focus on the mechanisms of activation and regulation of these pathways in the context of rheumatic diseases and Alzheimer’s disease.

Host: Johannes SCHMID

Contact for questions: Helmut KUBISTA