Original Research ARTICLE
Persistent intracellular Staphylococcus aureus in keratinocytes lead to activation of the complement system with subsequent reduction in the intracellular bacterial load
- 1Department of Clinical sciences Lund, Lund University, Sweden
- 2Department of Clinical sciences Lund, Skåne University Hospital, Lund University, Sweden
- 3Department of Clinical Immunology, Copenhagen University Hospital, Denmark
- 4Leo pharma (Denmark), Denmark
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 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 Staphylococcus aureus infection of epidermal keratinocytes resulted in complement activation. Using fluorescence microscopy, we found that persistent Staphylococcus aureus, surviving intracellularly in keratinocytes, caused activation of the complement system with formation of the terminal complement complex at the cell surface. Skin samples from atopic dermatitis patients analyzed by bacterial culture and microscopy, demonstrated that Staphylococcus aureus colonization was associated with the presence of intracellular bacteria and deposition of the terminal complement complex 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 illustrates a novel mechanism by which the complement system combats persistent intracellular bacteria in epithelial cells
Keywords: Complement Activation, Membrane attack complex, classical pathway activation, Intracellular infection, Staphylococcus aureus, atopic dermatitis, Erk activation
Received: 21 Nov 2017;
Accepted: 13 Feb 2018.
Edited by:José R. Mineo, Federal University of Uberlandia, Brazil
Reviewed by:Catherine A. Brissette, University of North Dakota, United States
Maryam Dadar, Razi Vaccine and Serum Research Institute, Iran
Copyright: © 2018 Abu-Humaidan, Elvén, Sonesson, Garred and Sørensen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: MD. Anas H. Abu-Humaidan, Lund University, Department of Clinical sciences Lund, Sölvegatan 19, BioMedical Centre, Lund, 22362, Skåne, Sweden, firstname.lastname@example.org