Endolysin Inhibits Skin Colonization by Patient-Derived Staphylococcus Aureus and Malignant T-Cell Activation in Cutaneous T-Cell Lymphoma
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Staphylococcus aureus is suspected to fuel disease activity in cutaneous T-cell lymphomas. In this study, we investigate the effect of a recombinant, antibacterial protein, endolysin (XZ.700), on S. aureus skin colonization and malignant T-cell activation. We show that endolysin strongly inhibits the proliferation of S. aureus isolated from cutaneous T-cell lymphoma skin and significantly decreases S. aureus bacterial cell counts in a dose-dependent manner. Likewise, ex vivo colonization of both healthy and lesional skin by S. aureus is profoundly inhibited by endolysin. Moreover, endolysin inhibits the patient-derived S. aureus induction of IFNγ and the IFNγ-inducible chemokine CXCL10 in healthy skin. Whereas patient-derived S. aureus stimulates activation and proliferation of malignant T cells in vitro through an indirect mechanism involving nonmalignant T cells, endolysin strongly inhibits the effects of S. aureus on activation (reduced CD25 and signal transducer and activator of transcription 5 phosphorylation) and proliferation (reduced Ki-67) of malignant T cells and cell lines in the presence of nonmalignant T cells. Taken together, we provide evidence that endolysin XZ.700 inhibits skin colonization, chemokine expression, and proliferation of pathogenic S. aureus and blocks their potential tumor-promoting effects on malignant T cells.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Investigative Dermatology |
Vol/bind | 143 |
Udgave nummer | 9 |
Sider (fra-til) | 1757-1769 |
Antal sider | 15 |
ISSN | 0022-202X |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This research was funded by the LEO Foundation, the Danish Cancer Society (Kræftens Bekæmpelse), the Fight Cancer Program (Knæk Cancer), Novo Nordisk Research Foundation, the Novo Nordisk Foundation Tandem Program (grant number NNF21OC0066950), and the Danish Council for Independent Research (Danmarks Frie Forskningsfond, two project grants). The authors wish to thank Neel Gerner and her collegues (Lyngby, Denmark) for valuable collaboration and help setting up skin cultures.
Publisher Copyright:
© 2023
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