Rocha-de-Souza Claudio M, Berent-Maoz Beata, Mankuta David, Moses Allon E, Levi-Schaffer Francesca
Department of Pharmacology and Experimental Therapeutics, Faculty of Medicine, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
Infect Immun. 2008 Oct;76(10):4489-97. doi: 10.1128/IAI.00270-08. Epub 2008 Jul 21.
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.
金黄色葡萄球菌侵入宿主细胞并在其中存活的能力被认为与其引发持续性和转移性感染的倾向有关。此外，金黄色葡萄球菌感染常与特应性疾病如皮炎、鼻炎和哮喘相关。肥大细胞是过敏性疾病的关键细胞，在固有免疫中起关键作用，具有吞噬能力，能破坏一些病原菌。然而，对于其他一些细菌在肥大细胞中存活并克服其吞噬作用的能力知之甚少。因此，我们有兴趣评估肥大细胞与金黄色葡萄球菌之间的相互作用。在本研究中，我们发现人脐血来源的肥大细胞（CBMC）可被致病性金黄色葡萄球菌感染。金黄色葡萄球菌对肥大细胞表现出高度的黏附性以及在其中的侵袭和存活能力。然而，当在细胞松弛素D存在的情况下进行感染时，或者当CBMC与抗Toll样受体2（TLR2）或抗CD48抗体预孵育时，侵袭性和炎症反应分别被消除。此外，我们观察到金黄色葡萄球菌感染后CBMC上TLR2和CD48分子增加。金黄色葡萄球菌感染CBMC还导致肿瘤坏死因子α（TNF-α）和白细胞介素-8（IL-8）的释放。活的和灭活的金黄色葡萄球菌均被发现能以时间依赖性方式触发CBMC释放TNF-α和IL-8。总的来说，这些发现表明金黄色葡萄球菌可内化并在肥大细胞中存活。这可能在与金黄色葡萄球菌相关的感染和特应性疾病中起重要作用。
