Multiple roles of Toll-like receptor signaling in atherosclerosis.
OBJECTIVE
Toll-like receptors are key regulators of both innate and adaptive immune responses. This review outlines the recently emerged multiple roles of Toll-like receptor signaling in atherosclerosis.


RESULTS
Mice deficient in TLR4, TLR2 and MyD88 all have reduced atherosclerosis which establishes that Toll-like receptor-dependent pathways contribute to disease development. Although it is likely that total "infectious burden" contributes to atherosclerosis progression, endogenous ligands may also initiate and modulate Toll-like receptor signaling pathways. CD36, with established roles in recognition of endogenous ligands and atherosclerotic disease, facilitates TLR2 signaling and might therefore represent a bridge between endogenous lipid ligands and Toll-like receptor pathways. Furthermore, lipoprotein oxidation generates ligands that activate Toll-like receptor pathways. At the same time, Toll-like receptor activation may be inhibited by accumulating oxidized phospholipids, which could result in reduced dendritic cell maturation and impaired immunological priming.


CONCLUSIONS
Activation of Toll-like receptor signaling can promote atherosclerosis by multiple mechanisms, while some beneficial Toll-like receptor pathways may be inhibited by lipid accumulation. Due to their central role in the disease process, Toll-like receptor signaling pathways represent a target of immunomodulatory therapy with the goal of tipping the balance from excessive chronic inflammation towards resolution of inflammation, while not compromising host defense or atheroprotective immune functions.
Björkbacka
Harry
H
Department of Clinical Sciences, Malmö University Hospital, Lund University, SE-205 02 Malmö, Sweden. harry.bjorkback@med.lu.se
D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism; D051379:Mice; D011110:Polymorphism, Genetic; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
D008024:Ligands; D051193:Toll-Like Receptors