Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation

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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) which induce cross-talk between malignant and benign T cells leading to Stat3-mediated 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.

Original languageEnglish
JournalBlood
Volume124
Issue number5
Pages (from-to)761-70
Number of pages10
ISSN0006-4971
DOIs
Publication statusPublished - 2014

ID: 117551050