Milovanović Ivan, Busarčević Miloš, Trbovich Alexander, Ivović Vladimir, Uzelac Aleksandra, Djurković-Djaković Olgica
Institute for Pathologic Physiology, School of Medicine, University of Belgrade, Belgrade, Serbia.
National Reference Laboratory for Toxoplasmosis, Center of Excellence for Food- and Vector-borne Zoonoses, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
PLoS One. 2017 May 1;12(5):e0176700. doi: 10.1371/journal.pone.0176700. eCollection 2017.
Toxoplasma gondii is one of the most successful parasites on Earth, infecting a wide array of mammals including one third of the global human population. The obligate intracellular protozoon is not capable of synthesizing cholesterol (Chl), and thus depends on uptake of host Chl for its own development. To explore the genetic regulation of previously observed lipid metabolism alterations during acute murine T. gondii infection, we here assessed total Chl and its fractions in serum and selected tissues at the pathophysiological and molecular level, and integrated the observed gene expression of selected molecules relevant for Chl metabolism, including its biosynthetic and export KEGG pathways, with the results of published transcriptomes obtained in similar murine models of T. gondii infection. The serum lipid status as well as the transcript levels of relevant genes in the brain and the liver were assessed in experimental models of acute and chronic toxoplasmosis in wild-type mice. The results showed that acute infection was associated with a decrease in Chl content in both the liver and periphery (brain, peripheral lymphocytes), and a decrease in Chl reverse transport. In contrast, in chronic infection, a return to normal levels of Chl metabolism has been noted. These changes corresponded to the brain and liver gene expression results as well as to data obtained via mining. We propose that the observed changes in Chl metabolism are part of the host defense response. Further insight into the lipid metabolism in T. gondii infection may provide novel targets for therapeutic agents.
弓形虫是地球上最成功的寄生虫之一，感染包括全球三分之一人口在内的多种哺乳动物。这种专性细胞内原生动物无法合成胆固醇（Chl），因此依赖摄取宿主胆固醇来实现自身发育。为了探索在急性小鼠弓形虫感染期间先前观察到的脂质代谢改变的遗传调控，我们在病理生理和分子水平评估了血清和选定组织中的总胆固醇及其组分，并将观察到的与胆固醇代谢相关的选定分子的基因表达（包括其生物合成和输出的KEGG途径）与在类似的小鼠弓形虫感染模型中获得的已发表转录组结果进行整合。在野生型小鼠的急性和慢性弓形虫病实验模型中评估了血清脂质状态以及大脑和肝脏中相关基因的转录水平。结果表明，急性感染与肝脏和外周组织（大脑、外周淋巴细胞）中胆固醇含量的降低以及胆固醇逆向转运的减少有关。相比之下，在慢性感染中，已观察到胆固醇代谢恢复到正常水平。这些变化与大脑和肝脏的基因表达结果以及通过挖掘获得的数据一致。我们认为观察到的胆固醇代谢变化是宿主防御反应的一部分。对弓形虫感染中脂质代谢的进一步深入了解可能为治疗药物提供新的靶点。
