Human mast cell activation by Staphylococcus aureus: Interleukin-8 and tumor necrosis factor alpha release and the role of toll-like receptor 2 and CD48 molecules

Department of Pharmacology and Experimental Therapeutics, Faculty of Medicine, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
Infection and immunity (Impact Factor: 4.16). 10/2008; 76(10):4489-97. DOI: 10.1128/IAI.00270-08
Source: PubMed

ABSTRACT The ability of Staphylococcus aureus to invade and survive within host cells is believed to contribute to its propensity to cause persistent and metastatic infections. In addition, S. aureus infections often are associated with atopic diseases such as dermatitis, rhinitis, and asthma. Mast cells, the key cells of allergic diseases, have a pivotal role in innate immunity and have the capacity of phagocytosis, and they can destroy some pathogenic bacteria. However, little is known about the ability of some other bacteria to survive and overcome mast cell phagocytosis. Therefore, we were interested in evaluating the interplay between mast cells and S. aureus. In this study, we show that human cord blood-derived mast cells (CBMC) can be infected by pathogenic S. aureus. S. aureus displayed a high adherence to mast cells as well as invasive and survival abilities within them. However, when infections were performed in the presence of cytochalasin D or when CBMC were preincubated with anti-Toll-like receptor 2 (TLR2) or anti-CD48 antibodies, the invasiveness and the inflammatory response were abrogated, respectively. Furthermore, we observed an increase of TLR2 and CD48 molecules on CBMC after S. aureus infection. The infection of CBMC with S. aureus also caused the release of tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8). Both live and killed S. aureus organisms were found to trigger TNF-alpha and IL-8 release by CBMC in a time-dependent manner. Cumulatively, these findings suggest that S. aureus internalizes and survives in mast cells. This may play an important role in infections and in atopic diseases associated with S. aureus.

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    Antonie van Leeuwenhoek 01/2015; 107(4). DOI:10.1007/s10482-015-0378-6 · 2.14 Impact Factor
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    ABSTRACT: Background Allergy is characterized by eosinophilia and an increased susceptibility to microbial infection. Atopic dermatitis (AD) is typically associated with Staphylococcus aureus (SA) colonization. Some of the mechanisms by which SA and its exotoxins interact with eosinophils remain elusive. CD48, a glycosylphosphatidylinositol-anchored receptor belonging to the CD2 family, participates in mast cells-SA stimulating cross-talk, facilitates the formation of the mast cell/eosinophils effector unit and as expressed by eosinophils, mediates experimental asthma.Objective To investigate the role of CD48 expressed on human peripheral blood and mouse bone marrow derived eosinophils (BMEos) in their interaction with heat-killed SA and its three exotoxins, SEB, PtA and PGN.Methods Eosinophils were obtained from human peripheral blood and BM of WT and CD48-/- mice. SA was heat killed and eosinophils-SA/exotoxins interactions were analyzed by confocal microscopy, adhesion and degranulation, cell viability, cytokine release and cell signaling. In addition, peritonitis was induced by SEB injection into CD48-/- and WT mice. CD48 expression was studied in AD patients’ skin and as expressed on their leukocytes in the peripheral blood.ResultsWe provide evidence for the recognition and direct physical interaction between eosinophils and SA/exotoxins. Skin of AD patients showed a striking increase of eosinophil associated CD48 expression while on peripheral blood leukocytes it was down-regulated. SA/exotoxins enhanced CD48 eosinophil expression, bound to CD48 and caused eosinophil activation and signal transduction. These effects were significantly decreased by blocking CD48 on human eosinophils or in BMEos from CD48-/- mice. We have also explored the role of CD48 in a SEB-induced peritonitis model in CD48-/- mice by evaluating inflammatory peritoneal cells, eosinophil numbers and activation.Conclusions These data demonstrate the important role of CD48 in SA/exotoxins-eosinophil activating interactions that can take place during allergic responses and indicate CD48 as a novel therapeutic target for allergy and especially of AD.This article is protected by copyright. All rights reserved.
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