Evaluation of the phagocytic and candidacidal activities of mast cells: involvement of toll-like 2 and dectin-1 receptors and NF-ºB signalling

• Grant number: 11/16838-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2012
• End date: February 28, 2014
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Vanessa Soares Lara
• Grantee: Karen Henriette Pinke
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

The pattern-recognition receptors of innate immunity are important in the defense against pathogens by recognizing conserved structures of microorganisms and triggering signaling pathways, such as nuclear factor-ºB (NF-ºB). This pathway may be triggered by the binding of the toll-like receptor 2 (TLR2) and dectin-1 receptor to their ligands, such as phospholipomannan and ²-glucans present in the cell wall of Candida albicans (C. albicans), a fungus commonly found in the mucosa of the gastrointestinal tract, including the oral mucosa, and can cause local or invasive candidiasis, especially in states of immunosuppression. Mast cells, which present these receptors on their cell membrane, reside at the interfaces with the environment and can be one of the first lines of defense against this fungus. The immune mechanisms of these cells include synthesis and secretion of mediators, antigen presentation, as well as phagocytic and microbicidal activities. All of these defense mechanisms can be triggered independently or cooperatively between TLR2 and dectin-1 receptor. This study aims to evaluate the occurrence of phagocytosis, the generation of ROS and RNS and the expression of TLR2, dectin-1 receptor and transcription factor NF-ºB by mast cells challenged or not in vitro with C. albicans. We also intend to evaluate the involvement of TLR2 and dectin-1 receptor in these events. To do this, mast cells, differentiated from bone marrow of wild-type or TLR2-/- mice, blocked or not with anti-dectin-1 receptor antibody, will be challenged with C. albicans. These events will be analyzed by confocal microscopy, Griess, DCFH-DA, MCLA and DAF-2-DA methods, flow cytometry and assay for nuclear transcription factor. Expression of results and statistical tests will be applied according to the presence or absence of normality in the evaluations (p<0.05).

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PINKE, KAREN HENRIETTE; DE LIMA, HELITON GUSTAVO; CUNHA, FERNANDO QUEIROZ; LARA, VANESSA SOARES. Mast cells phagocyte Candida albicans and produce nitric oxide by mechanisms involving TLR2 and Dectin-1. Immunobiology, v. 221, n. 2, p. 220-227, FEB 2016. (10/18779-6, 09/14152-1, 11/16838-8)

Academic Publications

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

PINKE, Karen Henriette. Participation of mast cells and its TLR2 and dectin-1 receptors in defense against C. albicans: phagocytosis and production/release of nitric oxide and hydrogen peroxide. 2014. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Odontologia de Bauru (FOB/SDB) Bauru.