NOD2-Induced IκBζ Mediates a Protective Host Response against Epicutaneous Staphylococcus aureus Infection.

Area of Science:

• Immunology
• Dermatology
• Microbiology

Background:

• IκBζ (Inhibitor of nuclear factor kappa-B zeta) is an atypical IκB family member involved in immune functions.
• The role of keratinocyte-derived IκBζ in skin defense against Staphylococcus aureus remains largely unexplored.

Purpose of the Study:

• To investigate the function of keratinocyte-derived IκBζ during infection with multidrug-resistant Staphylococcus aureus.
• To elucidate the signaling pathway regulating IκBζ expression and its contribution to host defense.

Main Methods:

• Keratinocyte infection models with Staphylococcus aureus.
• Analysis of gene and protein expression (antimicrobial peptides, IL-17/IL-36 responsive genes, skin barrier proteins).
• In vivo studies using mouse models to assess skin infection severity and immune cell recruitment.

Main Results:

• Staphylococcus aureus infection rapidly induced IκBζ expression in keratinocytes.
• IκBζ expression promoted antimicrobial peptides, IL-17/IL-36 responsive genes, and skin barrier proteins.
• Loss of IκBζ increased bacterial internalization, epidermal damage, and infection severity, with reduced immune cell recruitment.
• NOD2 (Nucleotide-binding oligomerization domain-containing protein 2) sensing of internalized S. aureus triggered IκBζ expression.

Conclusions:

• NOD2-IκBζ signaling is a critical pathway for protective skin immunity against Staphylococcus aureus.
• IκBζ plays a vital role in keratinocyte-mediated defense against bacterial skin infections.