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Interaction of Toxoplasma gondii lectins with natural killer Toll like receptors

Grant number: 17/17289-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2017
Effective date (End): October 31, 2018
Field of knowledge:Biological Sciences - Immunology - Immunochemistry
Principal researcher:Maria Cristina Roque Antunes Barreira
Grantee:Irislene Simões Brigo
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/04088-0 - Lectin from pathogens, AP.TEM

Abstract

Toxoplasma gondii (T.gondii), a coccidian member of the Apicomplexa phylum infects approximately one-third of the world's human population. Toxoplasma gondii infects host cells actively, a process that necessarily involves a release of lectins, called microneme proteins (TgMICs), originating from intracellular organelles. TgMIC1, TgMIC4 and TgMIC6 form a complex on the surface of T. gondii, which allows adhesion of the parasite to the host cell, through recognition of carbohydrates, since TgMIC1 binds to terminal sialic acid and TgMIC4 to terminal galactose. The presence of glycans associated with Toll-like receptors motivated the hypothesis that they could be targets for the carbohydrate recognition domains (CRD) of T.gondii microneme proteins. This hypothesis has been confirmed by recent studies, in which recombinant forms of TgMIC1 and TgMIC4 were used to stimulate HEK293 cells transfected with TLR4 or TLR2; It was found that TgMIC1 and TgMIC4 activate TLR4 and TLR2, in the presence or absence of co-receptors and accessory molecules. Additionally, TgMIC1 and TgMIC4, also induces IL-12 cytokine levels, in dependence of TLR2 and TLR4. IL-12 production is critical for T. gondii infection because this cytokine induces T cells and natural killer (NK) to produce IFN-³, which plays a crucial role in host protection [4]. NK cells are an important source of IFN-³, although the mechanism, by which they are activated during T.gondii infection, is still unknown. Studies demonstrate that as NK cells encode members of the Toll-like receptor family, such as, TLR1, TLR2, TLR3, TLR4 and TLR6. Thus, it is valid to suppose that microneme proteins 1 and 4 interact with Toll receptors on the surface of NK cells, leading to its activity and production of IFN-g. It is also possible that the cell response is influenced by synergistic signals generated by other innate immunity cells, such as macrophages and dendritic cells, when activated with TgMICs. In this project, these hypotheses will be rigorously investigated. It is expected that these efforts will result in a better understanding of the parasite infection process and the immune response generated by T. gondii antigens.Voltar (AU)

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