Toll-like receptors in atherosclerosis: a ‘Pandora's box’ of advances and controversies

• Atherosclerosis is an inflammatory disorder with a strong involvement of innate immunity.
• Toll-like receptors (TLRs) are key components of the innate immune system.
• Recent evidence suggests that TLRs elicit both protective and detrimental roles in atherosclerosis.
• Emerging data suggests that the outcome of TLR signaling is agonist- and cell type-dependent.
• This review aims to update and explore controversies of the role of TLRs in atherosclerosis.

Seminal research over the past 20 years has revealed atherosclerosis to be a chronic inflammatory process that shares features with traditional inflammatory diseases including rheumatoid arthritis. More recently, emphasis has been placed on the role of innate immunity in the development and progression of atherosclerosis. In particular, pattern recognition receptors, including Toll-like receptors (TLRs), have been the focus of much attention as modulators of atherogenesis. This review provides an update on the developments in this area of research in the past 2 years, with a specific focus on the current controversies and how these may affect the design of therapeutics. Specifically, we will address the recent evidence that TLRs elicit both protective and detrimental effects in atherosclerosis and the emerging observation that the outcome of TLR signaling is dependent on the agonist and responding cell type.