Staphylococcus aureus Second Immunoglobulin-Binding Protein drives atopic dermatitis via IL-33

Arwa Al Kindi, Helen Williams, Kenshiro Matsuda, Abdullah Alkahtani, Charis Saville, Hayley Bennett, Yasmine Alshammari, Soo Y. Tan, Catherine O'Neill, Akane Tanaka, Hiroshi Matsuda, Peter Arkwright, Joanne Pennock

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Background: S. aureus is the dominant infective trigger of atopic dermatitis (AD). How this bacterium drives type 2 allergic pathology in the absence of infection in AD patients is unclear.
Objective: To identify the S. aureus-derived virulence factor(s) that initiates the cutaneous type 2-promoting immune response responsible for AD.
Methods: In vitro human keratinocyte cell culture, ex vivo human skin organ explants and the eczema prone Nc/Tnd mouse were used as model systems to assess type-2 promoting immune responses to S. aureus. Identification of the bioactive factor was accomplished using Fast Protein Liquid Chromatography and mass spectrometry. Bioactivity was confirmed by cloning and expression in an E. coli vector system, and S. aureus Sbi mutant strains confirming loss of activity.
Results: S. aureus was unique amongst staphylococcal species in its ability to induce the rapid release of constitutive IL-33 from human keratinocytes independent of the toll-like receptor pathway. Using the eczema-prone NC/Tnd mouse model, we showed that IL-33 was essential in inducing the immune response to S. aureus in vivo. By fractionation and candidate testing, we identified the Second Immunoglobulin-Binding Protein (Sbi) as the predominant staphylococcus-derived virulence factor that directly drives IL-33 release from human keratinocytes. Immunohistology of skin demonstrated that corneodesmosin, a component of corneodesmosomes that form key intercellular adhesive structures in the stratum corneum, was disrupted resulting in reduction of skin barrier function.
Conclusion: S. aureus-derived Sbi is a unique type 2-promoting virulence factor capable of initiating the type-2 promoting cytokine activity underlying AD.
Original languageEnglish
Article number0
Pages (from-to)1354-1368.e3
JournalJournal of Allergy and Clinical Immunology
Issue number4
Publication statusPublished - Apr 2021


  • IL-33
  • Sbi
  • Staphylococcus aureus
  • TSLP
  • atopic dermatitis
  • keratinocytes
  • second immunoglobulin-binding protein
  • skin
  • type 2 immune response
  • virulence factor

Research Beacons, Institutes and Platforms

  • Lydia Becker Institute


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