TY  - JOUR
AU  - Fischer, Berenice
AU  - Kolb, Antonia
AU  - Focaccia, Enrico
AU  - Kübelbeck, Tanja
AU  - Klein, Matthias
AU  - Löck, Dagmar
AU  - Bork, Francesca
AU  - Engelmann, Franziska
AU  - Casari, Martina
AU  - Mazza, Elisa
AU  - Deppermann, Carsten
AU  - Weber, Alexander N R
AU  - Wittmann, Miriam
AU  - Schittek, Birgit
AU  - Schulze-Osthoff, Klaus
AU  - Kramer, Daniela
TI  - NOD2-induced IκBζ mediates a protective host response against epicutaneous Staphylococcus aureus infection.
JO  - The journal of investigative dermatology
VL  - nn
SN  - 0022-202X
CY  - Amsterdam
PB  - Elsevier
M1  - DKFZ-2025-01086
SP  - nn
PY  - 2025
N1  - epub
AB  - IκBζ, an atypical and largely unknown member of the IκB family, is a transcriptional coactivator of selective immune functions. Here, we investigated the role of keratinocyte-derived IκBζ upon infection with a multidrug-resistant S. aureus strain. Infection of keratinocytes rapidly induced IκBζ expression, leading to an elevated expression of antimicrobial peptides, IL-17/IL-36-responsive genes, and proteins involved in skin barrier function. Conversely, loss of IκBζ resulted in increased S. aureus internalization, epidermal tissue damage, and severe skin infections in vivo. This impaired host defense upon IκBζ depletion was characterized by reduced antimicrobial peptide expression, and diminished recruitment of neutrophils and CD4+ T-cells. Importantly, S. aureus-induced IκBζ expression required the internalization of the bacteria and its sensing by the intracellular receptor NOD2, which triggered IκBζ and its target gene expression. Thus, we identified NOD2-IκBζ signaling as a novel pathway acting as a key mediator for a protective host defense against pathogenic S. aureus infections in the skin.
KW  - IκBζ (Other)
KW  - NFKBIZ (Other)
KW  - NOD2 (Other)
KW  - Staphylococcus aureus (Other)
KW  - TLR2 (Other)
KW  - keratinocytes (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40412468
DO  - DOI:10.1016/j.jid.2025.04.036
UR  - https://inrepo02.dkfz.de/record/301578
ER  -