An Important Role of α-Hemolysin in Extracellular Vesicles on the Development of Atopic Dermatitis Induced by Staphylococcus aureus

• Published in: PloS one Vol. 9; no. 7; p. e100499
• Main Authors: Hong, Sung-Wook, Choi, Eun-Byul, Min, Taek-Ki, Kim, Ji-Hyun, Kim, Min-Hye, Jeon, Seong Gyu, Lee, Byung-Jae, Gho, Yong Song, Jee, Young-Koo, Pyun, Bok-Yang, Kim, Yoon-Keun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.07.2014; Public Library of Science (PLoS)
• Subjects: Animals; Annexin V; Apoptosis; Atopic dermatitis; Bacterial Proteins - immunology; Biology and Life Sciences; Cell death; Cell Line; Cytotoxicity; Dermatitis; Dermatitis, Atopic - immunology; Dermatitis, Atopic - pathology; Diagnostic systems; Disease; Disruption; Eczema; Extracellular vesicles; Gene expression; Gram-positive bacteria; Hemolysin Proteins - immunology; Humans; Hyperplasia; Keratinocytes; Keratinocytes - immunology; Keratinocytes - pathology; Life sciences; Medicine; Medicine and Health Sciences; Mice; Mice, Hairless; Pathogenesis; Pathogens; Pediatrics; Skin; Skin - immunology; Skin - pathology; Staphylococcal Skin Infections - immunology; Staphylococcal Skin Infections - pathology; Staphylococcus aureus; Staphylococcus aureus - immunology; Staphylococcus infections; Therapeutic applications; Toxins; Vesicles; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0100499

Skin barrier disruption and dermal inflammation are key phenotypes of atopic dermatitis (AD). Staphylococcus aureus secretes extracellular vesicles (EVs), which are involved in AD pathogenesis. Here, we evaluated the role of EVs-associated α-hemolysin derived from S. aureus in AD pathogenesis. α-hemolysin production from S. aureus was detected using western blot analyses. The cytotoxic activity of α-hemolysin on HaCaT keratinocytes was evaluated by measuring cell viability after treating cells with soluble and EVs-associated α-hemolysin. To determine the type of cell death, HaCaT keratinocytes were stained with annexin V and 7-AAD. The in vivo effects of α-hemolysin were evaluated by application of soluble and EV-associated α-hemolysin on the mouse skin. The present study showed that increased α-hemolysin was produced by S. aureus colonized on AD patients compared to healthy subjects. α-hemolysin production was also related to AD severity. In addition, EV-associated α-hemolysin was more cytotoxic to HaCaT keratinocytes than soluble α-hemolysin, and α-hemolysin-negative EVs did not induce keratinocyte death. EV-associated α-hemolysin induced necrosis, but soluble α-hemolysin induced apoptosis of keratinocytes. In vivo, skin barrier disruption and epidermal hyperplasia were induced by soluble and EV-associated α-hemolysin. However, AD-like dermal inflammation was only caused by EV-associated α-hemolysin. Moreover, neither skin barrier disruption nor AD-like skin inflammation was induced by α-hemolysin-negative EVs. Taken together, α-Hemolysin secreted from S. aureus, particularly the EV-associated form, induces both skin barrier disruption and AD-like skin inflammation, suggesting that EV-associated α-hemolysin is a novel diagnostic and therapeutic target for the control of AD.