The effect of a self-limited leishmania major infection on atherogenesis in C57BL/6 mice

Abstract

Atherosclerosis, the most common cardiovascular disease, is a chronic disorder characterized by the accumulation of oxidized LDL in the macrophages leading to the formation of foam cells and then atherosclerotic plaques which rupture or not according to the immune response of the host. C57BL/6 mice represent a susceptible strain for high fat diet induced atherosclerosis. They develop an immune response characterized by the production of proinflammatory cytokines characteristic of Th1 cells especially IFN-γ and Th17 cytokines like IL-17 which also has a proatherogenic role, while the role of Th2 cytokines in atherosclerosis is less understood, some studies consider them as atheroprotective. Another important and widespread disease is Leishmaniasis which is divided into 3 types: cutaneous, mucocutaneous and visceral. Experimental studies use usually L.major strain which belongs to the cutaneous type. C57BL/6 mice are considered as resistant for leishmaniasis meaning that they develop a Th1 response all over the infection course with limited production of IL-4, the key cytokine of Th2 cells in the early phase of the disease. This characteristic may have a certain effect on diet induced atherosclerosis. In the current project, we aim to investigate the effect of L.major infection on high fat diet induced atherosclerosis in C57BL/6 mice. Therefore, C57BL/6 mice were divided into four groups: NF group which is a control fed with a regular diet without infection with L.major, NFL group fed with a regular diet and injected with high dose L.major, HF group fed with a high fat diet without any injection and the last one is HFL group fed with a high fat diet and injected with a high dose L.major. We performed ELISA for plasma and the aortas homogenates of these mice; it has shown a significant increase in Th1 key cytokine IFN-γ at an early time (3 weeks) in the plasma with maintenance of this cytokine all over the experiment in the aorta. In addition, IL-4, the main cytokine of Th2 cells was undetectable in the aortas of HFL group. Moreover, IL-17 which is produced by different cell types especially Th17 was also released at an early time in both plasma and aorta of HFL group (3week).