Malignant T Cell Activation by a Bacillus Species Isolated from Cutaneous T-Cell Lymphoma Lesions

Carina A Dehner; William E Ruff; Teri Greiling; Márcia S Pereira; Sylvio Redanz; Jennifer McNiff; Michael Girardi; Martin A Kriegel

doi:10.1016/j.xjidi.2021.100084

Malignant T Cell Activation by a Bacillus Species Isolated from Cutaneous T-Cell Lymphoma Lesions

JID Innov. 2021 Dec 16;2(2):100084. doi: 10.1016/j.xjidi.2021.100084. eCollection 2022 Mar.

Authors

Carina A Dehner^{1

2}, William E Ruff¹, Teri Greiling^{1

3}, Márcia S Pereira⁴, Sylvio Redanz⁴, Jennifer McNiff⁵, Michael Girardi⁶, Martin A Kriegel^{1

4

7}

Affiliations

¹ Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
² Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
³ Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA.
⁴ Department of Translational Rheumatology and Immunology, Institute of Musculoskeletal Medicine, University of Münster, Münster, Germany.
⁵ Department of Dermatopathology, Yale University School of Medicine, New Haven, Connecticut, USA.
⁶ Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA.
⁷ Section of Rheumatology and Clinical Immunology, Department of Medicine, University Hospital Münster, Münster, Germany.

Abstract

Cutaneous T-cell lymphoma (CTCL) is a life-debilitating malignancy of lymphocytes homing to the skin. Although CTCL is thought to arise from a combination of genetic, epigenetic, and environmental factors, specific triggers are unclear. The skin is colonized by a unique microbiota and is heavily influenced by its interactions. We hypothesized that adaptive immune responses to skin commensals lead to clonal T-cell proliferation and transformation in the appropriate genetic background. We therefore collected lesional and nonlesional skin microbiota from patients with CTCL to study T cell interactions using skin T cell explants and peripheral, skin-homing CD4⁺ T cells. By various methods, we identified Bacillus safensis in CTCL lesions, a rare human commensal in healthy skin, and showed that it can induce malignant T cell activation and cytokine secretion. Taken together, our data suggest microbial triggers in the skin microbiota of patients with CTCL as potential instigators of tumorigenesis.

Keywords: ASV, amplicon sequence variant; CLA, cutaneous lymphocyte‒associated antigen; CTCL, cutaneous T-cell lymphoma; MF, mycosis fungoides; STAT3, signal transducer and activator of transcription 3; rRNA, ribosomal RNA.

Abstract

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