Mast cells phagocyte Candida albicans and produce nitric oxide by mechanisms involving TLR2 and Dectin-1

Author(s)

Pinke, Karen Henriette ^[1] ; de Lima, Heliton Gustavo ^[1] ; Cunha, Fernando Queiroz ^[2] ; Lara, Vanessa Soares ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Stomatol, Bauru Sch Dent, Al Dr Octavio Pinheiro Brisola 9-75, BR-17012901 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Med Sch, Al Dr Octavio Pinheiro Brisola 9-75, BR-17012901 Sao Paulo - Brazil

• Document type: Journal article
• Source: Immunobiology; v. 221, n. 2, p. 220-227, FEB 2016.
• Web of Science Citations: 18

Abstract

Candida albicans (C. albicans) is a fungus commonly found in the human mucosa, which may cause superficial and systemic infections, especially in immunosuppression. Until now, the main actors in the defense against this fungus are the epithelial cells, neutrophils, macrophages/monocytes and dendritic cells. However, mast cells are strategically located to play a first line of anti-Candida defense and it has appropriate mechanisms to do it. As with other cells, the recognition of C. albicans occurs meanly via TLR2 and Dectin-1. We assess the TLR2/Dectin-1 involvement in phagocytosis and production of nitric oxide (NO) and reactive oxygen species (ROS) by mast cells challenged with C. albicans. Bone marrow-derived mast cells (MC) from wild type (Wt) or knockout (TLR2-/-) mice C57BL/6 were subjected to in vitro Dectin-1 blockade. After challenged with FITC-labeled C. albicans or zymosan, phagocytosis was analyzed by microscopy. The intracellular production of NO and ROS was measured by DAF-FM diacetate and CelIROX Deep/Red Reagent kits. The nitrite formation and hydrogen peroxide release were analyzed by Griess reaction and Amplex Red Hydrogen Peroxide/Peroxidase Assay Kit. Wt/MC phagocytose C albicans with production of intracellular NO, but not ROS. Moreover, increased levels of nitrite were also observed. The absence and/or blockade of TLR2/Dectin-1 caused significant decreased in C. albicans phagocytosis and NO production. Our results showed that mast cells are able to phagocytose and produce NO against C. albicans via TLR2/Dectin-1. Therefore, mast cells could be important during the course of Candida infection and as a therapeutic target. (C) 2015 Elsevier GmbH. All rights reserved. (AU)

• FAPESP's process: 10/18779-6 - Defense mechanisms of mast cells against Candida albicans: involvement of Toll-like 2 receptor in phagocytic activity.
• Grantee: Karen Henriette Pinke
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 09/14152-1 - Defense mechanisms of mast cells against Candida albicans: involvement of Toll-like 2 receptor in the production of cytokines TNF-alpha and IL-10, and the phagocytic and antimicrobial activities
• Grantee: Vanessa Soares Lara
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/16838-8 - Evaluation of the phagocytic and candidacidal activities of mast cells: involvement of toll-like 2 and dectin-1 receptors and NF-ºB signalling
• Grantee: Karen Henriette Pinke
• Support Opportunities: Scholarships in Brazil - Master