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Cholesterol  2013 

Leishmania major Self-Limited Infection Increases Blood Cholesterol and Promotes Atherosclerosis Development

DOI: 10.1155/2013/754580

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Leishmania major infection of resistant mice causes a self-limited lesion characterized by macrophage activation and a Th1 proinflammatory response. Atherosclerosis is an inflammatory disease involving hypercholesterolemia and macrophage activation. In this study, we evaluated the influence of L. major infection on the development of atherosclerosis using atherosclerosis-susceptible apolipoprotein E-deficient (apoE KO) mice. After 6 weeks of infection, apoE KO mice exhibited reduced footpad swelling and parasitemia similar to C57BL/6 controls, confirming that both strains are resistant to infection with L. major. L. major-infected mice had increased plasma cholesterol levels and reduced triacylglycerols. With regard to atherosclerosis, noninfected mice developed only fatty streak lesions, while the infected mice presented with advanced lesions containing a necrotic core and an abundant inflammatory infiltrate. CD36 expression was increased in the aortic valve of the infected mice, indicating increased macrophage activation. In conclusion, L. major infection, although localized and self-limited in resistant apoE KO mice, has a detrimental effect on the blood lipid profile, increases the inflammatory cell migration to atherosclerotic lesions, and promotes atherogenesis. These effects are consequences of the stimulation of the immune system by L. major, which promotes the inflammatory components of atherosclerosis, which are primarily the parasite-activated macrophages. 1. Introduction Leishmania major is a protozoan parasite transmitted by sandflies of the genus Lutzomyia that inject the promastigote form into the dermis of the host. Once injected, the parasite is rapidly enclosed by phagocytic cells and transforms into the replicative intracellular amastigote form [1]. In immunocompetent hosts, such as C57BL/6 mice, L. major infection is a self-contained cutaneous lesion that elicits a Th1 immune response. In infected mice, the immune cells (macrophages, dendritic cells, natural killer cells, and T cells) produce cytokines and bioactive molecules, such as IFN-γ, IL-12, and nitric oxide (NO), which act against the protozoan [1]. Atherosclerosis is a chronic inflammatory disease associated with a high level of total cholesterol and proatherogenic lipoproteins (VLDL, IDL, and LDL), a prothrombotic status, and a Th1-polarized immune response [2, 3]. Macrophage and endothelial cell activation by atypical lipoproteins and proinflammatory cytokines induces the production of adhesion molecules, cytokines and chemokines, and causes oxidative stress [4]. Among


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