Persistent intracellular Staphylococcus aureus in keratinocytes lead to activation of the complement system with subsequent reduction in the intracellular bacterial load

Research output: Contribution to journalArticle

Abstract

The complement system is an ancient part of the innate immune system important for both tissue homeostasis and host defense. However, bacteria like Staphylococcus aureus (SA) possess elaborative mechanisms for evading both the complement system and other parts of the immune system. One of these evasive mechanisms-important in causing chronic and therapy resistant infections-is the intracellular persistence in non-immune cells. The objective of our study was to investigate whether persistent intracellular SA infection of epidermal keratinocytes resulted in complement activation. Using fluorescence microscopy, we found that persistent SA, surviving intracellularly in keratinocytes, caused activation of the complement system with formation of the terminal complement complex (TCC) at the cell surface. Skin samples from atopic dermatitis patients analyzed by bacterial culture and microscopy, demonstrated that SA colonization was associated with the presence of intracellular bacteria and deposition of the TCC in epidermis in vivo. Complement activation on keratinocytes with persistent intracellular bacteria was found with sera deficient/depleted of the complement components C1q, Mannan-binding lectin, or complement factor B, demonstrating involvement of more than one complement activation pathway. Viable bacterial counts showed that complement activation at the cell surface initiated cellular responses that significantly reduced the intracellular bacterial burden. The use of an inhibitor of the extracellular signal-regulated kinase (ERK) abrogated the complement-induced reduction in intracellular bacterial load. These data bridge the roles of the complement system in tissue homeostasis and innate immunity and illustrate a novel mechanism by which the complement system combats persistent intracellular bacteria in epithelial cells.

Details

Authors
Organisations
External organisations
  • Copenhagen University Hospital
  • Leo Pharma A/S
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

Keywords

  • Atopic dermatitis, Classical pathway activation, Complement activation, Erk activation, Intracellular infection, Membrane attack complex, Staphylococcus aureus
Original languageEnglish
Article number396
JournalFrontiers in Immunology
Volume9
Issue numberMAR
Publication statusPublished - 2018 Mar 1
Publication categoryResearch
Peer-reviewedYes

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Research output: ThesisDoctoral Thesis (compilation)

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