title: Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation.
abstract: Patients with cutaneous T-cell lymphoma (CTCL) are frequently colonized with Staphylococcus aureus (SA). Eradication of SA is, importantly, associated with significant clinical improvement, suggesting that SA promotes the disease activity, but the underlying mechanisms remain poorly characterized. Here, we show that SA isolates from involved skin express staphylococcal enterotoxins (SEs) that induce crosstalk between malignant and benign T cells leading to Stat3-mediated interleukin-10 (IL-10) production by the malignant T cells. The SEs did not stimulate the malignant T cells directly. Instead, SEs triggered a cascade of events involving cell-cell and asymmetric cytokine interactions between malignant and benign T cells, which stimulated the malignant T cells to express high levels of IL-10. Much evidence supports that malignant activation of the Stat3/IL-10 axis plays a key role in driving the immune dysregulation and severe immunodeficiency that characteristically develops in CTCL patients. The present findings thereby establish a novel link between SEs and immune dysregulation in CTCL, strengthening the rationale for antibiotic treatment of colonized patients with severe or progressive disease.
authors: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;
authors: Thorbjørn
authors: T
authors: Krejsgaard
authors: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;
authors: Andreas
authors: A
authors: Willerslev-Olsen
authors: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark;
authors: Lise M
authors: LM
authors: Lindahl
authors: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;
authors: Charlotte M
authors: CM
authors: Bonefeld
authors: Department of Pathology, New York University School of Medicine, New York, NY;
authors: Sergei B
authors: SB
authors: Koralov
authors: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;
authors: Carsten
authors: C
authors: Geisler
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA;
authors: Mariusz A
authors: MA
authors: Wasik
authors: Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark; and.
authors: Robert
authors: R
authors: Gniadecki
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Mogens
authors: M
authors: Kilian
authors: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark;
authors: Lars
authors: L
authors: Iversen
authors: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;
authors: Anders
authors: A
authors: Woetmann
authors: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;
authors: Niels
authors: N
authors: Odum
mesh_terms: D001426:Bacterial Proteins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004768:Enterotoxins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000473:pathology; D008297:Male; D050796:STAT3 Transcription Factor / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology / Q000473:pathology; D013211:Staphylococcus aureus; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; D004768:Enterotoxins; C508609:IL10 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10