title: Leishmania major Self-Limited Infection Increases Blood Cholesterol and Promotes Atherosclerosis Development.
abstract: 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.
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Luciana R
authors.initials: LR
authors.lastname: Fernandes
authors.forename: Ana Cecília C
authors.initials: AC
authors.lastname: Ribeiro
authors.forename: Marcela
authors.initials: M
authors.lastname: Segatto
authors.forename: Luís Felipe F F
authors.initials: LF
authors.lastname: Santos
authors.forename: Joana
authors.initials: J
authors.lastname: Amaral
authors.forename: Luciane R
authors.initials: LR
authors.lastname: Portugal
authors.forename: Jacqueline I A
authors.initials: JI
authors.lastname: Leite