Role of TLR9 in Atherosclerosis? Therapeutic ODN in heart disease?

Atherosclerosis is the underlying pathology of diseases such as coronary artery disease resulting in major overall mortality and morbidity. It is a chronic inflammatory disease of the arterial wall in which the innate immune system has a pivotal contribution. Toll-like receptor-9 (TLR9) is a major intracellular innate immune receptor that has attracted major interest and is currently clinically tested as a therapeutic target of inflammatory diseases. Using apolipoprotein E–deficient mice fed with high-fat diet during periods of 8 to 20 weeks as a model of atherosclerosis we used a genetic (TLR9 deletion) and a pharmacological approach (TLR9 agonist) to demonstrate a protective role of TLR9 in atherosclerosis. We describe the modulation of cell numbers and inflammatory phenotype of CD4+ T cells as a potential mechanism. Moreover we have identified a novel and attractive therapeutic approach to attenuate progression of atherosclerotic disease based on the use of TLR9-activating CpG oligodeoxynucleotides.