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The role of N-WASP, WAVE2 and cortactin in the internalization by extracellular amastigotes of Trypanosoma cruzi in professional phagocytic cells (THP-1)

Grant number: 17/20432-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2017
Effective date (End): October 31, 2019
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Renato Arruda Mortara
Grantee:Camila Macedo Medina
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:16/15000-4 - Trypanosoma cruzi: intra and interspecific genomic variability and mechanisms of cell invasion/egress, AP.TEM

Abstract

Chagas disease is caused by the flagellate protozoan Trypanosoma cruzi and affects around 6 to 7 million people worldwide. T. cruzi cell invasion can occur by metacyclic and blood trypomastigote forms and extracellular amastigote forms (EAs) which is originated by premature lysis of host cell or by extracellular differentiation of bloodstream trypomastigotes. EAs are able to invade and colonize professional and non-professional phagocytic cells and are able to sustain the cycle in the vertebrate host. It is known that invasion of these forms is highly dependent on host cells actin cytoskeleton, and the mobilization of actin to invasion site is an orchestrated process involving several components of both: parasite and host cell, especially molecules that regulate the actin cytoskeleton. In this context, cortactin, N-WASP and WAVE2 proteins are known for their participation regulating actin cytoskeleton dynamics also phagocytosis process and have been described for their involvement in EA internalization in non-professional phagocytic cells (NPF), reinforcing the idea that EAs induce phagocytosis of the host cell thereby promoting its invasion. In order to investigate whether the processes described in NPF cells during EAs invasion are present in professional phagocytic cells (THP-1), the present project aims to investigate whether cytoskeleton associated proteins such cortactin, N-WASP and WAVE2 are important to EA internalization in phagocytic cells (THP-1). Thus bringing more evidences that EAs promote in non-phagocytic cells an specialized machinery able to induce phagocytosis and consequent internalization. (AU)