New diagnostic strategies employed in symptomatic toxoplasmosis

Abstract

The aim of this project will be the study of the AIDS-toxoplasmosis co-infection, which is the most prevalent opportunistic neurological disease in Brazil. Particularity, we will study some parasite-host relationship patterns. A part of the investigations will be devoted to the study of cytokine gene expression in patients with AIDS- cerebral toxoplasmosis co-infection. The studies will be correlated with the evolution of the encoding genes for IFN³, IL4 and IL12 cytokines. The experiments will be made in clinical samples from patients. The results will be analyzed to establish or not the possible inhibitory mechanism of these cytokine syntheses. In parallel, we will study topics of the disseminated toxoplasmosis performing in a retrospective investigation. We will analyze samples from autopsies of 15 patients who had died with confirmed histological diagnosis for disseminated toxoplasmosis. Cytokine profiles in brain and lung tissue will be evaluated in situ. Dopamine levels in the brain tissue will be also evaluated. Next, we intend to correlate possible behavior changes, since studies suggest T. gondii may be interfering in the dopamine production in infected hosts. At the same time, T. gondii genotyping from DNA extracted from paraffin-embedded tissue samples will be performed. This project, also, will investigate the gene expression profile of microRNA (miRNA) among strains with different virulence of T. gondii , and whether T. gondii miRNA can modulate the levels of host micro RNA during infection by identifying their presence in the different forms of the parasite and the host. miRNAs have been recently described and composes a noncoding small RNAs that regulate gene expression of thousands of genes. The miRNA is exported from the cells by vesicles called exosomes and may be present in biological fluids including blood, urine, and cell culture medium. Overall, the results generated in this project will generate data for a better understanding of the cellular response in patients with cerebral toxoplasmosis and those with disseminated disease with a poor prognosis. The study of T. gondii miRNA may contribute to understand whether these molecules may interfere with infection or whether they mediate host miRNA. The knowledge of this data could be prospect for the use of miRNA in the diagnosis of infection. (AU)