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: 3.73). 10/2008; 76(10):4489-97. DOI: 10.1128/IAI.00270-08
Source: PubMed


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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Available from: David Mankuta, Jul 21, 2015
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    • "The direct interaction is primarily mediated by pattern recognition receptors (PRRs), including TLRs (as discussed in 4) by Toll-like receptor ligands, C-type lectins such as Dectin-1, retinoic acid-inducible gene-I-like receptors (RLRs) and the glycosylphosphatidylinositol-anchored protein CD48 (Abraham and St John, 2010; Urb and Sheppard, 2012). For instance, Dectin-1 can induce leukotriene production from hCBMC in response to fungal zymosan (Olynych et al., 2006); RLRs together with TLR3 stimulate LAD2 cells to produce type-I IFNs and chemokines by interacting with vesicular stomatitis virus (VSV) (Tsutsui-Takeuchi et al., 2014); CD48 activates mast cell by recognizing fimbriated Escherichia coli (in mBMMCs), Mycobacterium tuberculosis (in RBL-2H3 and mouse peritoneal mast cells) or Staphylococcus aureus (in hCBMC) (Malaviya et al., 1999; Munoz et al., 2003; Rocha-de-Souza et al., 2008). The indirect mechanism includes Fc-receptor-and complement-receptor-mediated interaction. "
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    ABSTRACT: Mast cells are crucial effector cells in allergic reactions, where IgE is the best known mechanism to trigger their degranulation and release of a vast array of allergic mediators. However, IgE is not the only component to stimulate these cells to degranulate, while mast cell activation can also result in differential release of mediators. There is a plethora of stimuli, such as IgG, complement components, TLR ligands, neuropeptides, cytokines, chemokines and other inflammatory products, that can directly trigger mast cell degranulation, cause selective release of mediators, and stimulate proliferation, differentiation and/or migration. Moreover, some of these stimuli have a synergic effect on the IgE-mediated mast cell activation. Because of the ability to respond to a large repertoire of stimuli, mast cells may act as a versatile cell in various physiological and pathological conditions. In this review, we discuss current knowledge on non-IgE stimuli for (human) mast cells. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 07/2015; DOI:10.1016/j.ejphar.2015.07.017 · 2.53 Impact Factor
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    • "Reports have described the participation of TLR2 during S. aureus internalization in NPPCs; however, the results are not conclusive because TLR2 participation in phagocytosis may be indirect. For example, Rocha-de-Souza et al. (2008) indicated that TLR2 is involved in S. aureus internalization into human cord blood-derived mast cells using neutralizing antibodies [26]. The blockage of TLR2 in these cells decreases the number of bacteria internalized. "
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    ABSTRACT: Staphylococcus aureus is a successful human and animal pathogen. The majority of infections caused by this pathogen are life threatening, primarily because S. aureus has developed multiple evasion strategies, possesses intracellular persistence for long periods, and targets the skin and soft tissues. Therefore, it is very important to understand the mechanisms employed by S. aureus to colonize and proliferate in these cells. The aim of this review is to describe the recent discoveries concerning the host receptors of nonprofessional phagocytes involved in S. aureus internalization. Most of the knowledge related to the interaction of S. aureus with its host cells has been described in professional phagocytic cells such as macrophages. Here, we showed that in nonprofessional phagocytes the α 5 β 1 integrin host receptor, chaperons, and the scavenger receptor CD36 are the main receptors employed during S. aureus internalization. The characterization and identification of new bacterial effectors and the host cell receptors involved will undoubtedly lead to new discoveries with beneficial purposes.
    BioMed Research International 04/2014; 2014:538546. DOI:10.1155/2014/538546 · 1.58 Impact Factor
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    • "Mast cells may play an important role in CRSwNP, as abundant degranulated mast cells were observed in tissue sections. After S. aureus infection, mast cells increase the amount of TLR2 receptors on their surface and consequently release of TNF-α and IL-8 [20]. PGN, lipoproteins, and lipoteichoic acid from S. aureus are able to stimulate mast cells directly via the binding of TLR2 on these cells. "
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    ABSTRACT: Staphylococcus aureus (S. aureus) is correlated with the development of persistent severe inflammatory disease of the upper airway including chronic rhinosinusitis with nasal polyps. This inflammation of the upper airways is characterized by a T-helper 2-driven disease: interleukin-5 is significantly increased and local production of immunoglobulin E is observed. S. aureus and its enterotoxins are deregulating the tissue inflammation at different levels: structural cells and the innate and adaptive immune system. Knowing the triggers of the pathomechanisms involved will greatly help us to find new therapeutic approaches to resolve this chronic inflammatory process.
    World Allergy Organization Journal 08/2010; 3(8):223-8. DOI:10.1097/WOX.0b013e3181ecd8ae
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