497 Staphylococcus aureus components increase Th2 response in cutaneous lymphoma

Abstract

Mycosis fungoides and Sezary Syndrome are the most common types of cutaneous T-cell Lymphomas (CTCL) and are often characterized by a Th2-dominant phenotype. This Th2 microenvironment is advantageous for tumor cells but may cause higher susceptibility to infections. Indeed, it has been shown that Staphylococcus aureus (S. aureus) frequently colonizes the skin and nares of CTCL patients which can result in chronic and recurrent skin and systemic infections. Furthermore, patients colonized by S. aureus who were treated with antibiotics frequently show clinical improvement of their skin lesion, suggesting a possible functional role of S. aureus in the pathogenesis and/or course of CTCL. We demonstrate that cell membrane components from S. aureus can increase Th2 cytokines production by tumor cells. Moreover, previous studies have revealed that S. aureus-derived microvesicles (MVs) carry a complex arsenal of virulence factors and toxins that allow better infection and serve host immunomodulatory functions. Furthermore, bacterial cell wall components such as peptidoglycans and lipoteichoic acid are part of the MV complex. We demonstrate that, when exposed to various S. aureus cell wall and MV components, human CTCL cell line (HUT78) increased expression of Th2 cytokines (IL-4 and IL-13) up to 20 and 80 fold, respectively (p≤0.001) and thymic stromal lymphopoeitin receptor (TSLPR) and IL7Ra by approximately five to ten fold (p≤0.05). TSLPR and IL7Ra form the heterodimeric receptor for TSLP, a cytokine able to promote Th2 differentiation in naïve T cells. These result suggest that S. aureus MV and cell wall components provide signals that may render CTCL cells more susceptible to TSLP effects. Together, our data shows that S. aureus components help CTCL to maintain a tumor-beneficial Th2 microenviroment. Understanding the role of S. aureus colonization in CTCL may contribute to better targets for future therapies.