期刊
FASEB JOURNAL
卷 35, 期 7, 页码 -出版社
WILEY
DOI: 10.1096/fj.201902836R
关键词
fibroblasts; staphyloccous aureus; wound healing
资金
- Prof. Max Cloetta Foundation
- Abbvie \ AbbVie Deutschland (AbbVie Germany)
- Novartis Stiftung fur Medizinisch-Biologische Forschung (Novartis Foundation for Medical-Biological Research)
- Olga Mayenfisch Foundation
- Vontobel-Stiftung (Vontobel Foundation)
- EMDO Stiftung (EMDO-Stiftung)
- Herzog Egli Foundation
- Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung (SNF) [31003A_176252]
The study revealed that Staphylococcus aureus affects dermal fibroblasts, leading to impaired tissue repair functions such as upregulation of pro-inflammatory cytokines and degradation of collagen. This impact is not limited to specific cell sources and affects key mechanisms of wound healing.
Chronic wounds are a major disease burden worldwide. The breach of the epithelial barrier facilitates transition of skin commensals to invasive facultative pathogens. Therefore, we investigated the potential effects of Staphylococcus aureus (SA) on dermal fibroblasts as key cells for tissue repair. In co-culture systems combining live or heat-killed SA with dermal fibroblasts derived from the BJ-5ta cell line, healthy individuals, and patients with systemic sclerosis, we assessed tissue repair including pro-inflammatory cytokines, matrix metalloproteases (MMPs), myofibroblast functions, and host defense responses. Only live SA induced the upregulation of IL-1 beta/-6/-8 and MMP1/3 as co-factors of tissue degradation. Additionally, the increased cell death reduced collagen production, proliferation, migration, and contractility, prerequisite mechanisms for wound closure. Intracellular SA triggered inflammatory and type I IFN responses via intracellular dsDNA sensor molecules and MyD88 and STING signaling pathways. In conclusion, live SA affected various key tissue repair functions of dermal fibroblasts from different sources to a similar extent. Thus, SA infection of dermal fibroblasts should be taken into account for future wound management strategies.
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