TY - JOUR TI - Staphylococcus aureus Second Immunoglobulin-Binding Protein drives atopic dermatitis via IL-33 AU - Kindi, Arwa Al AU - Williams, Helen AU - Matsuda, Kenshiro AU - Alkahtani, Abdullah M. AU - Saville, Charis AU - Bennett, Hayley AU - Alshammari, Yasmine AU - Tan, Soo Y. AU - O’Neill, Catherine AU - Tanaka, Akane AU - Matsuda, Hiroshi AU - Arkwright, Peter D. AU - Pennock, Joanne L. T2 - Journal of Allergy and Clinical Immunology AB -

Abstract

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.

Clinical Implications

The Second Immunoglobulin-Binding Protein (Sbi) produced solely by S. aureus species, is an important factor inducing type-2 promoting cytokine responses and atopic dermatitis.

DA - 2020/09/30/ PY - 2020 DO - 10.1016/j.jaci.2020.09.023 DP - www.jacionline.org VL - 0 IS - 0 J2 - Journal of Allergy and Clinical Immunology LA - English SN - 0091-6749, 1097-6825 UR - https://www.jacionline.org/article/S0091-6749(20)31335-X/abstract Y2 - 2020/10/05/16:53:45 ER -