High-density lipoprotein (HDL) plays a major role in vasodilation and in the reduction of low-density lipoprotein (LDL) oxidation, inflammation, apoptosis, thrombosis, and infection; however, HDL is now less functional in these roles under certain conditions. This paper focuses on HDL, its anti-inflammation behavior, and the mechanisms by which HDL interacts with components of the innate and adaptive immune systems. Genome-wide association studies (GWAS) and proteomic studies have elucidated important molecules involved in the interaction between HDL and the immune system. An understanding of these mechanisms is expected to be useful for the prevention and treatment of chronic inflammation due to metabolic syndrome, atherosclerosis, or various autoimmune diseases. 1. Introduction High-density lipoprotein (HDL) contains free or esterified cholesterol, phospholipids, triglycerides, and various proteins, including apolipoproteins, enzymes, and transfer proteins. The most abundant HDL apolipoproteins are apoA-I and apoA-II; less abundant are apoC, apoE, apoD, and apoJ. HDL enzymes include lecithin:cholesterol acyltransferase (LCAT), serum paraoxonase-1 (PON1) [1–3], and platelet-activating factor acetylhydrolase (PAF-AH) . Transfer proteins include cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP). Furthermore, chromatography and mass spectrometry have revealed many other proteins in HDL [5, 6]. HDL particles can be subclassified into small discoidal HDL (pre-β1 HDL and pre-β2 HDL), intermediate spherical ( , , and ), and large, cholesterol-rich spherical ( and ) [7–10] (Figure 1). Large particles interact with liver scavenger receptors class B type 1 (SR-B1), which ensures the delivery of cholesterol to the liver . Intermediate induces cholesterol efflux through the ATP-binding cassette transporter G1 (ABCG1) . Small HDL particles promote cholesterol efflux through the ATP-binding cassette transporter A1 (ABCA1) . Accumulating evidence suggests that in addition to reverse transport of cholesterol from the periphery to the liver, HDL plays a major role in vasodilation and in the reduction of LDL oxidation , inflammation, apoptosis, thrombosis, and infection . During infection, both innate and adaptive immunities are involved in the inflammatory process and the immune response. Innate immunity is a nonspecific defense mechanism comprising cellular and humoral responses. The cellular response includes antigen-presenting cells such as macrophage and dendritic cells. The humoral response includes various
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