Journal Article

Evidence for host genetic regulation of altered lipid metabolism in experimental toxoplasmosis supported with gene data mining results

Trbovich, Alexander, Busarčević, Miloš, Djurković-Djaković, Olgica, Ivović, Vladimir, Uzelac, Aleksandra, Milovanović, Ivan

2017

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animal models / Animals / Apolipoproteins / Atherosclerosis / Biology and Life Sciences / Brain / Brain - metabolism / Brain research / Chemical compounds / Chlamydia / Cholesterol / Cholesterol - metabolism / Chronic infection / Computer and Information Sciences / Data Mining / Data processing / Diagnosis / Female / Food / Gene expression / Gene Expression Regulation / Genetic aspects / Genetic diversity / Genetic regulation / Health aspects / Homeostasis - genetics / Host-Parasite Interactions - genetics / Host-Parasite Interactions - physiology / Human populations / Infections / Laboratories / Lipid metabolism / Lipid Metabolism - genetics / Lipids / Liver / Liver - metabolism / Low density lipoprotein / Lymphocytes / Mammals / Medical research / Medicine and Health Sciences / Metabolism / Mice / Microarray Analysis / Parasites / Pharmacology / Physiology / Real-Time Polymerase Chain Reaction / Research and Analysis Methods / RNA, Messenger - metabolism / Rodents / Tissues / Toxoplasma - physiology / Toxoplasmosis / Toxoplasmosis, Animal - genetics / Toxoplasmosis, Animal - metabolism / Transcription / Transcriptome / Triglycerides - metabolism / Vectors (Biology) / Zoonoses