Biphasic influence of Staphylococcus aureus on human epidermal tight junctions

TY - JOUR

T1 - Biphasic influence of Staphylococcus aureus on human epidermal tight junctions

AU - Bäsler, Katja

AU - Galliano, Marie-Florence

AU - Bergmann, Sophia

AU - Rohde, Holger

AU - Wladykowski, Ewa

AU - Vidal-Y-Sy, Sabine

AU - Guiraud, Beatrice

AU - Houdek, Pia

AU - Schüring, Germar

AU - Volksdorf, Thomas

AU - Caruana, Antony

AU - Bessou-Touya, Sandrine

AU - Schneider, Stefan W

AU - Duplan, Hélène

AU - Brandner, Johanna M

N1 - © 2017 New York Academy of Sciences.

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1111/nyas.13418

DO - 10.1111/nyas.13418

M3 - SCORING: Journal article

C2 - 28753223

VL - 1405

SP - 53

EP - 70

JO - ANN NY ACAD SCI

JF - ANN NY ACAD SCI

SN - 0077-8923

IS - 1

ER -