Patients with reactivation of toxoplasmic retinochoroiditis (RTR) can be classified as high, intermediate or low producers of gamma interferon (IFN-γ), the main molecule of the Th-1 cellular immune response against the Toxoplasma gondii parasite, based on IFN-γ release assays performed using peripheral blood mononuclear cells (PBMC). Similar results can be obtained by studying the genetic polymorphisms of IFN-γ, its receptor or the study of the genetic polymorphisms of the interleukin-10 (IL-10) gene. High levels of intraocular IFN-γ have been associated with a shorter time of evolution of RRT and without severe complications.
On the other hand, not all patients behave in the same way in each RTR episode (in terms of clinical course or response to treatment) despite their IFN-γ production capacity. Consequently, these assays are not yet of clinical use due to their limited capacity to predict chronic intraocular inflammation and/or complications. MicroRNAs or miRNAs are capable of modifying the immune response of patients, independently of their genetic polymorphisms, since they degrade the target messenger RNAs, thus decreasing the expression of specific proteins of the immune response against the parasite (epigenetic modification).
The present project is aimed at studying the changes in the expression of miRNAs in the CLMNP of patients whose IFN-γ expression profile we already know. The following project aims to compare the miRNA profiles in patients with RTR vs inactive scar toxoplasmosis and compare these groups with negative control individuals for T. gondii infection. The stimulation of the CLMNP will be performed with lysate from two very phylogenetically divergent strains, ME49 (clonal II) or TgCkAr 11-9 (non-clonal I-III, isolation prevalence in Misiones), with the objective of obtaining expression profiles of different miRNAs.
On the other hand, not all patients behave in the same way in each RTR episode (in terms of clinical course or response to treatment) despite their IFN-γ production capacity. Consequently, these assays are not yet of clinical use due to their limited capacity to predict chronic intraocular inflammation and/or complications.
MicroRNAs or miRNAs are capable of modifying the immune response of patients, independently of their genetic polymorphisms, since they degrade target messenger RNAs, thus decreasing the expression of specific proteins of the immune response against the parasite (epigenetic modification).
In this project we intend to study changes in the expression of miRNAs in the CLMNP of patients in whom we already know their IFN-γ expression profile. The following project aims to compare the miRNA profiles of patients with RTR vs inactive scar toxoplasmosis and compare these groups with negative control individuals for T. gondii infection. The stimulation of the CLMNP will be performed with lysate from two very phylogenetically divergent strains, ME49 (clonal II) or TgCkAr 11-9 (non-clonal I-III, prevalent isolate in Misiones) hoping to obtain expression profiles of different miRNAs.
Keywords: Ocular toxoplasmosis, miRNA, chronic inf
Start date: 2022-02-01
