Harvard Medical School, Boston, MA, USA.
Virulence. 2010 Jul-Aug;1(4):223-35. doi: 10.4161/viru.1.4.11466.
Staphylococcus aureus is a leading cause of invasive infection. It also infects wet mucosal tissues including the cornea and conjunctiva. Conflicting evidence exists on the expression of Toll-like receptors by human corneal epithelial cells. It was therefore of interest to determine how epithelial cells from this immune privileged tissue respond to S. aureus. Further, it was of interest to determine whether cytolytic toxins, with the potential to cause ion flux or potentially permit effector molecule movement across the target cell membrane, alter the response. Microarrays were used to globally assess the response of human corneal epithelial cells to S. aureus. A large increase in abundance of transcripts encoding the antimicrobial dendritic cell chemokine, CCL20, was observed. CCL20 release into the medium was detected, and this response was found to be largely TLR2 and NOD2 independent. Corneal epithelial cells also respond to S. aureus by increasing the intracellular abundance of mRNA for inflammatory mediators, transcription factors, and genes related to MAP kinase pathways, in ways similar to other cell types. The corneal epithelial cell response was surprisingly unaffected by toxin exposure. Toxin exposure did, however, induce a stress response. Although model toxigenic and non-toxigenic strains of S. aureus were employed in the present study, the results obtained were strikingly similar to those reported for stimulation of vaginal epithelial cells by clinical toxic shock toxin expressing isolates, demonstrating that the initial epithelial cellular responses to S. aureus are largely independent of strain as well as epithelial cell tissue source.
金黄色葡萄球菌是一种主要的侵袭性感染病原体。它还会感染湿性粘膜组织，包括角膜和结膜。目前对于人角膜上皮细胞表达 Toll 样受体的情况存在相互矛盾的证据。因此，确定这种免疫特权组织的上皮细胞对金黄色葡萄球菌的反应如何是很有趣的。此外，确定是否细胞溶解毒素（有可能导致离子通量或允许效应分子穿过靶细胞膜移动）会改变反应，这也很有趣。微阵列用于全面评估人角膜上皮细胞对金黄色葡萄球菌的反应。观察到编码抗菌树突状细胞趋化因子 CCL20 的转录本丰度大量增加。检测到 CCL20 释放到培养基中，并且发现这种反应在很大程度上独立于 TLR2 和 NOD2。角膜上皮细胞还通过增加细胞内炎性介质、转录因子和与 MAP 激酶途径相关的基因的 mRNA 丰度来对金黄色葡萄球菌作出反应，其方式与其他细胞类型相似。毒素暴露对角膜上皮细胞的反应出人意料地没有影响。然而，毒素暴露确实会诱导应激反应。尽管本研究中使用了模型产毒和非产毒金黄色葡萄球菌菌株，但获得的结果与临床毒性休克毒素表达分离株刺激阴道上皮细胞的结果惊人地相似，表明人角膜上皮细胞对金黄色葡萄球菌的初始上皮细胞反应在很大程度上独立于菌株以及上皮细胞组织来源。
