Biphasic influence of Staphylococcus aureus on human epidermal tight junctions
Biphasic influence of Staphylococcus aureus on human epidermal tight junctions
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DOI：
10.1111/nyas.13418
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发表时间：
2017-10-01
影响因子：
5.2
通讯作者：
Brandner, Johanna M.
中科院分区：
文献类型：
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作者：
Baesler, Katja;Galliano, Marie-Florence;Brandner, Johanna M.
细菌感染（如金黄色葡萄球菌）是皮肤屏障受损的严重问题，例如特应性皮炎患者。先前的研究表明，紧密连接（TJ）蛋白受到葡萄球菌感染的影响，角化细胞HaCaT感染后TJ功能受损。然而，在细胞或更类似于人类皮肤的模型中进行的功能研究还缺失。因此，我们研究了金黄色葡萄球菌在原代人角质形成细胞和重建人表皮（RHE）中的定殖和感染情况。我们发现短期接种导致TJ屏障功能增加，这在HaCaT细胞中没有发现，这暗示了早期的保护作用。这伴随着occludin磷酸化和occludin和claudin-4在细胞膜上的持续定位。长期孵育导致claudin-1和claudin-4在细胞膜上的存在减少，TJ屏障功能下降。金黄色葡萄球菌的agr调控作用是增加而不是减少。由于金黄色葡萄球菌接种而产生的促炎细胞因子影响这两个阶段。综上所述，我们在这里表明，金黄色葡萄球菌可以对TJ屏障有短期的促进作用，而从长期来看，它会导致TJ的紊乱。
Bacterial infections (e.g., with Staphylococcus aureus) are serious problems in skin with a compromised barrier, such as in patients with atopic dermatitis. Previously, it was shown that tight junction (TJ) proteins are influenced by staphylococcal infection, and TJ function is impaired after infection of the keratinocyte cell line HaCaT. However, functional studies in cells or models more similar to human skin are missing. Therefore, we investigated bacterial colonialization and infection with live S. aureus in primary human keratinocytes and reconstructed human epidermis (RHE). We show that short-term inoculation results in increased TJ barrier function-which could not be seen in HaCaT cells-hinting at an early protective effect. This is accompanied by occludin phosphorylation and sustained localization of occludin and claudin-4 at cell membranes. Long-term incubation resulted in decreased presence of claudin-1 and claudin-4 at cell membranes and decreased TJ barrier function. The agr regulon of S. aureus plays a role in the increasing but not in the decreasing effect. Proinflammatory cytokines, which are produced as a result of S. aureus inoculation, influence both phases. In summary, we show here that S. aureus can have short-term promoting effects on the TJ barrier, while in the long term it results in disturbance of TJs.