Persistent Intracellular Staphylococcus aureus in Keratinocytes Lead to Activation of the Complement System with Subsequent Reduction in the Intracellular Bacterial Load
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 evas...
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00396/full |
| _version_ | 1818239904681820160 |
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| author | Anas H. Abu-Humaidan Malin Elvén Andreas Sonesson Peter Garred Ole E. Sørensen Ole E. Sørensen |
| author_facet | Anas H. Abu-Humaidan Malin Elvén Andreas Sonesson Peter Garred Ole E. Sørensen Ole E. Sørensen |
| author_sort | Anas H. Abu-Humaidan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T13:04:58Z |
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| id | doaj.art-f6d3ba2ee39747e095c7d6c6c759cd57 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T13:04:58Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f6d3ba2ee39747e095c7d6c6c759cd572022-12-22T00:23:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00396332617Persistent Intracellular Staphylococcus aureus in Keratinocytes Lead to Activation of the Complement System with Subsequent Reduction in the Intracellular Bacterial LoadAnas H. Abu-Humaidan0Malin Elvén1Andreas Sonesson2Peter Garred3Ole E. Sørensen4Ole E. Sørensen5Department of Clinical Sciences Lund, Infection Medicine, Lund University, Lund, SwedenSkåne University Hospital, Department of Clinical Sciences Lund, Dermatology and Venereology, Lund University, Lund, SwedenSkåne University Hospital, Department of Clinical Sciences Lund, Dermatology and Venereology, Lund University, Lund, SwedenLaboratory of Molecular Medicine, Department of Clinical Immunology Section 7631, Copenhagen University Hospital, Rigshospitalet, Copenhagen, DenmarkSkåne University Hospital, Department of Clinical Sciences Lund, Dermatology and Venereology, Lund University, Lund, SwedenLeo Pharma A/S, Ballerup, DenmarkThe 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.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00396/fullcomplement activationmembrane attack complexclassical pathway activationintracellular infectionStaphylococcus aureusatopic dermatitis |
| spellingShingle | Anas H. Abu-Humaidan Malin Elvén Andreas Sonesson Peter Garred Ole E. Sørensen Ole E. Sørensen Persistent Intracellular Staphylococcus aureus in Keratinocytes Lead to Activation of the Complement System with Subsequent Reduction in the Intracellular Bacterial Load Frontiers in Immunology complement activation membrane attack complex classical pathway activation intracellular infection Staphylococcus aureus atopic dermatitis |
| title | Persistent Intracellular Staphylococcus aureus in Keratinocytes Lead to Activation of the Complement System with Subsequent Reduction in the Intracellular Bacterial Load |
| title_full | Persistent Intracellular Staphylococcus aureus in Keratinocytes Lead to Activation of the Complement System with Subsequent Reduction in the Intracellular Bacterial Load |
| title_fullStr | Persistent Intracellular Staphylococcus aureus in Keratinocytes Lead to Activation of the Complement System with Subsequent Reduction in the Intracellular Bacterial Load |
| title_full_unstemmed | Persistent Intracellular Staphylococcus aureus in Keratinocytes Lead to Activation of the Complement System with Subsequent Reduction in the Intracellular Bacterial Load |
| title_short | Persistent Intracellular Staphylococcus aureus in Keratinocytes Lead to Activation of the Complement System with Subsequent Reduction in the Intracellular Bacterial Load |
| title_sort | persistent intracellular staphylococcus aureus in keratinocytes lead to activation of the complement system with subsequent reduction in the intracellular bacterial load |
| topic | complement activation membrane attack complex classical pathway activation intracellular infection Staphylococcus aureus atopic dermatitis |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00396/full |
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