title: 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.
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.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Faculty of Medicine, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Claudio M
authors.initials: CM
authors.lastname: Rocha-de-Souza
authors.forename: Beata
authors.initials: B
authors.lastname: Berent-Maoz
authors.forename: David
authors.initials: D
authors.lastname: Mankuta
authors.forename: Allon E
authors.initials: AE
authors.lastname: Moses
authors.forename: Francesca
authors.initials: F
authors.lastname: Levi-Schaffer
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D001422:Bacterial Adhesion; D000071178:CD48 Antigen; D002478:Cells, Cultured; D003593:Cytoplasm / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology* / Q000382:microbiology*; D050296:Microbial Viability; D013211:Staphylococcus aureus / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C508606:CXCL8 protein, human; D016209:Interleukin-8; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha