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Phagocytosis and microbicidal activity against Candida albicans in THP-1 AIRE 1 deficient cells

Grant number: 11/02751-8
Support type:Scholarships in Brazil - Master
Effective date (Start): September 01, 2011
Effective date (End): February 28, 2013
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher:Antonio Condino Neto
Grantee:Marina Uchôa Wall Barbosa de Carvalho
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


A key feature of innate immunity is the involvement of receptors that recognize characteristic structures of microbial pathogens. These receptors are known as pattern recognition receptors (PRR). Possibly the most studied types are the Toll Like Receptors (TLR), however, there are other receptors that fulfill a similar function, with distinct structure of TLRs. Of these, dectin-1 receptor is considered the most important, and has also been the focus of intense research in recent years, emerging as a model receptor distinct from TLRs. Our group recently demonstrated that the AIRE protein is important for the signaling pathway of dectin-1 (critical for response to C. albicans), and the absence of AIRE leads to defects in the activation of the transcriptional factor NF-kB. We also demonstrated that AIRE interacts with molecules that compose the main signaling pathway of dectin-1. In this project, our proposal is to assess how the absence of AIRE protein influences specific and important events during the stimulation via dectin-1 as the production of reactive oxygen derivatives through the NADPH-oxidase system and microbicidal activity. This will bring much more precise information of the events involved in ROS formation by NADPH-oxidase activation via dectin-1, as well as the possible mechanism by which C. albicans undergoes phagocytosis and intracellular killing, contributing to the advancement of knowledge about the innate immune response to C. albicans. For the development of this project we will use the techniques of anion superoxide quantification, DHR reduction and microbicidal activity in phagocytes of human myelomonocytic THP-1-AIRE deficient protein. (AU)

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