Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation

Thorbjørn Frej Krejsgaard; Andreas Willerslev-Olsen; Lise Maria Lindahl; Charlotte Menne Bonefeld; Sergei B. Koralov; Carsten Geisler; Mariusz A. Wasik; Robert Gniadecki; Mogens Kilian; Lars Iversen; Anders Woetmann Andersen; Niels Ødum

doi:10.1182/blood-2014-01-551184

Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation

Thorbjørn Frej Krejsgaard, Andreas Willerslev-Olsen, Lise Maria Lindahl, Charlotte Menne Bonefeld, Sergei B. Koralov, Carsten Geisler, Mariusz A. Wasik, Robert Gniadecki, Mogens Kilian, Lars Iversen, Anders Woetmann Andersen, Niels Ødum

Department of Immunology and Microbiology

32 Citations (Scopus)

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.

Original language	English
Journal	Blood
Volume	124
Issue number	5
Pages (from-to)	761-70
Number of pages	10
ISSN	0006-4971
DOIs	https://doi.org/10.1182/blood-2014-01-551184
Publication status	Published - 31 Jul 2014

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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.",

author = "Krejsgaard, {Thorbj{\o}rn Frej} and Andreas Willerslev-Olsen and Lindahl, {Lise Maria} and Bonefeld, {Charlotte Menne} and Koralov, {Sergei B.} and Carsten Geisler and Wasik, {Mariusz A.} and Robert Gniadecki and Mogens Kilian and Lars Iversen and Andersen, {Anders Woetmann} and Niels {\O}dum",

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year = "2014",

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day = "31",

doi = "10.1182/blood-2014-01-551184",

language = "English",

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T1 - Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation

AU - Krejsgaard, Thorbjørn Frej

AU - Willerslev-Olsen, Andreas

AU - Lindahl, Lise Maria

AU - Bonefeld, Charlotte Menne

AU - Koralov, Sergei B.

AU - Geisler, Carsten

AU - Wasik, Mariusz A.

AU - Gniadecki, Robert

AU - Kilian, Mogens

AU - Iversen, Lars

AU - Andersen, Anders Woetmann

AU - Ødum, Niels

PY - 2014/7/31

Y1 - 2014/7/31

N2 - 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.

AB - 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.

U2 - 10.1182/blood-2014-01-551184

DO - 10.1182/blood-2014-01-551184

M3 - Journal article

C2 - 24957145

SN - 0006-4971

VL - 124

SP - 761

EP - 770

JO - Blood

JF - Blood

IS - 5

ER -

Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation

Abstract

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