Phenol-soluble modulins α are major virulence factors of Staphylococcus aureus secretome promoting inflammatory response in human epidermis

Virulence

Gérard Lina¹  Julien Verdon²  Luc Deroche³  Alexia Damour³  Brandon Robin³  Charles Bodet³  Nicolas Bellin³  Franck Marie Leclère⁴  Julie Cremniter⁵  Lauranne Broutin⁵  Nicolas Lévêque⁶  Magali Garcia⁶ 

[1] CIRI Centre International de Recherche en Infectiologie, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, Lyon, Franc;Centre National de Référence des Staphylocoques, Institut des Agent Infectieux, Hôpital de La Croix Rousse, Hospices Civils de Lyon, Lyon, Franc;Laboratoire Ecologie et Biologie des Interactions, UMR CNRS 7267, Université De Poitiers, Poitiers, Franc;Laboratoire Inflammation Tissus Epithéliaux et Cytokines EA 4331, Université De Poitiers, Poitiers, Franc;Laboratoire Inflammation Tissus Epithéliaux et Cytokines EA 4331, Université De Poitiers, Poitiers, Franc;Département de Chirurgie Plastique, Reconstructive et Esthétique, CHU de Poitiers, Poitiers, Franc;Laboratoire Inflammation Tissus Epithéliaux et Cytokines EA 4331, Université De Poitiers, Poitiers, Franc;Laboratoire De Bactériologie, CHU de Poitiers, Poitiers, Franc;Laboratoire Inflammation Tissus Epithéliaux et Cytokines EA 4331, Université De Poitiers, Poitiers, Franc;Laboratoire de Virologie et Mycobactériologie, CHU de Poitiers, Poitiers, Franc;

关键词: Staphylococcus aureus;    atopic dermatitis;    phenol soluble modulins;    inflammatory response;    keratinocyte;    epidermis;    toxins;    PSM α3;   

DOI  :  10.1080/21505594.2021.1975909

来源: Taylor & Francis

【 摘 要 】

Staphylococcus aureus is a skin commensal microorganism commonly colonizing healthy humans. Nevertheless, S. aureus can also be responsible for cutaneous infections and contribute to flare-up of inflammatory skin diseases such as atopic dermatitis (AD), which is characterized by dysbiosis of the skin microbiota with S. aureus as the predominant species. However, the role of major virulence factors of this pathogen such as phenol-soluble modulin (PSM) toxins in epidermal inflammation remains poorly understood. Stimulation of primary human keratinocytes with sublytic concentrations of synthetic and purified PSM α3 resulted in upregulation of a large panel of pro-inflammatory chemokine and cytokine gene expression, including CXCL1, CXCL2, CXCL3, CXCL5, CXCL8, CCL20, IL-1α, IL-1β, IL-6, IL-36γ and TNF-α, while inducing the release of CXCL8, CCL20, TNF-α and IL-6. In addition, using S. aureus culture supernatant from mutants deleted from genes encoding either α-type PSMs or all PSM production, PSMs were shown to be the main factors of S. aureus secretome responsible for pro-inflammatory mediator induction in human keratinocytes. On the other hand, α-type PSM-containing supernatant triggered an intense induction of pro-inflammatory mediator expression and secretion during both topical and basal layer stimulation of an ex vivo model of human skin explants, a physiologically relevant model of pluristratified epidermis. Taken together, the results of this study show that PSMs and more specifically α-type PSMs are major virulence factors of S. aureus inducing a potent inflammatory response during infection of the human epidermis and could thereby contribute to AD flare-up through exacerbation of skin inflammation.

【 授权许可】

CC BY