Staphylococcus aureus impairs dermal fibroblast functions with deleterious effects on wound healing.

Yokota, Masaya; Häffner, Nicola; Kassier, Matthew; Brunner, Matthias; Shambat, Srikanth Mairpady; Brennecke, Fabian; Schniering, Janine; Marques Maggio, Ewerton; Distler, Oliver; Zinkernagel, Annelies Sophie; Maurer, Britta (2021). Staphylococcus aureus impairs dermal fibroblast functions with deleterious effects on wound healing. FASEB journal, 35(7), e21695. Federation of American Societies for Experimental Biology 10.1096/fj.201902836R

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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-1β/-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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology

UniBE Contributor:

Maurer, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0892-6638

Publisher:

Federation of American Societies for Experimental Biology

Language:

English

Submitter:

Brigitte Isenschmid

Date Deposited:

28 Dec 2021 10:16

Last Modified:

05 Dec 2022 15:55

Publisher DOI:

10.1096/fj.201902836R

PubMed ID:

34160101

Uncontrolled Keywords:

fibroblasts staphyloccous aureus wound healing

BORIS DOI:

10.48350/161817

URI:

https://boris.unibe.ch/id/eprint/161817

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