Evaluation of the role of micronucleus 1 and 4 proteins in the immunopathology of Toxoplasmosis

• Grant number: 19/07411-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2019
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Maria Cristina Roque Antunes Barreira
• Grantee: Igor Emiliano Lemos de Souza
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Toxoplasmosis, a disease caused by the obligate intracellular protozoan Toxoplasma gondii, is considered a public and veterinary health concern. T. gondii can infect different nucleated cells of homeothermic animals. On the initial phase of cell infection, the parasite uses proteins present in unique organelles - micronemes and rhoptries - from its apical portion to actively penetrate the host cell. T. gondii microneme proteins (MICs) are critical in the early stages of cell invasion, acting on the adhesion and movement of the protozoan. In a recent study, our group reported that MIC1 binds to oligosaccharides from Toll-Like Receptors (TLRs), specifically from TLR2 and TLR4, and triggers cell signaling that induces to the production of interleukin 12, a pivotal cytokine to control T. gondii infection. However, there was a limitation in these studies in vivo because it was used RH strain that causes the death of the mouse in a few days, make possible to investigate only the early stages of the infection. To overcome this limitation, we recently obtained Wild-Type (WT) and MIC1, MIC4, and MIC1/MIC4 knockout T. gondii CZ1 strain, which is a cystogenic one. Thus, this work aims to determine whether mouse infections with WT or MICs knockout parasites of the CZ1 strain differ in immunopathological aspects in the acute and chronic infection phases. Besides, we will investigate whether the infection of human peripheral blood mononuclear cells or human cell lines with parasites of CZ1 strain WT ou MICs knockout has similar secreted cytokine profile to that verified in murine cells. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SOUZA, Igor Emiliano Lemos de. Toxicity of Toxoplasma gondii proteins MIC1 and MIC4 on human T cell lines. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.