Neutrophil extracellular traps enhance S. aureus skin colonization by oxidative stress induction and downregulation of epidermal barrier genes

Autor: Jule Focken, Jasmin Scheurer, Annika Jäger, Christian M. Schürch, Sofie Kämereit, Simon Riel, Martin Schaller, Bettina Weigelin, Birgit Schittek
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 10, Pp 113148- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.113148
Popis: Summary: Staphylococcus aureus is the most common cause of bacterial skin infections in humans, including patients with atopic dermatitis (AD). Polymorphonuclear neutrophils (PMNs) are the first cells to infiltrate an infection site, where they usually provide an effective first line of defense, including neutrophil extracellular trap (NET) formation. Here, we show that infiltrating PMNs in inflamed human and mouse skin enhance S. aureus skin colonization and persistence. Mechanistically, we demonstrate that a crosstalk between keratinocytes and PMNs results in enhanced NET formation upon S. aureus infection, which in turn induces oxidative stress and expression of danger-associated molecular patterns such as high-mobility-group-protein B1 (HMGB1) in keratinocytes. In turn, HMGB1 enhances S. aureus skin colonization and persistence by promoting skin barrier dysfunctions by the downregulation of epidermal barrier genes. Using patient material, we show that patients with AD exhibit enhanced presence of PMNs, NETs, and HMGB1 in the skin, demonstrating the clinical relevance of our finding.
Databáze: Directory of Open Access Journals