CD1d AS A NOVEL REGULATOR OF INNATE IMMUNITY

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Toll-like receptors (TLR) are a group of proteins that play a key role in the immune system by functioning as a first barrier for the recognition of pathogens such as virus or bacteria. The recognition of such pathogens by TLRs initiates a cascade of activation of immune cells that ultimately leads to pathogen elimination. However, the inappropriate activation of TLRs can be detrimental for health as in the case of autoimmune diseases or sepsis. Thus, understanding the processes that control the activation of TLRs is critical to modulate the balance between protective and pathogenic immune responses. Recent studies have proposed a role for the lipid cholesterol as a key regulator of TLR signalling. This suggests that controlling the cholesterol synthesis pathways (for instance by using statins) could be a tool to potentiate or dampen immune responses. However, the detailed processes regulating the crosstalk between immune cell activation and cholesterol metabolism remain unclear. The main aim of this proposal is to understand the pathways that link cholesterol metabolism and TLR responses. We will study in-depth the pathways that control TLR activation, investigate how they relate to cholesterol metabolism and evaluate their function during bacterial infection. Understanding the mechanisms regulating TLR activation will help design better strategies for prevention and treatment of infectious and inflammatory diseases.