Mast Cells Stimulated with Peptidoglycan from Staphylococcus aureus Augment the Development of Th1 Cells

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Background: The skin of patients with atopic dermatitis (AD) is superficially colonized by Staphylococcus aureus. We have previously found that percutaneous permeation of peptidoglycan (PEG) from S. aureus increases the number of mast cells in the dermis, as seen in skin lesions of AD patients. The purpose of the present study was to clarify the influence of PEG on T helper type 1 (Th1)/ T helper type 2 (Th2) cell development mediated by mast cells. Methods: Mast cells were induced by long-term culture of murine spleen cells in medium supplemented with tumor necrosis factor (TNF)- a. Ovalbumin (OVA) peptide-pulsed mast cells were incubated with naïve Th cells in the presence or absence of PEG. Five days later, Th cells in the culture were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and Th1/Th2 cytokine production was investigated by enzyme-linked immunosorbent assay. Results: It was confirmed that the mast cells we obtained had surface expression of I-Ad, worked as antigen-presenting cells, and induced Th1 cell and Th2 cell development. The stimulation of mast cells with PEG enhanced the development of Th1 cells but not that of Th2 cells. The increase of Th1 cell development stimulated by PEG was associated with an increase in the expression of Notch ligand Delta 1 in the mast cells. Furthermore, treatment of mast cells with the macrolide antibiotic josamycin suppressed Th1 cell development and this was correlated with a reduction of both Delta 1 expression and interleukin (IL)-12 production in mast cells. Conclusions: Colonization of S. aureus on the lesioned skin of AD patients contributes to not only an increase in the number of mast cells but also Th1 cell development mediated by mast cells in the dermis and subsequent induction of chronic inflammation, which is characterized by up-regulation of the Th1 cytokine, interferon (IFN)- g. Therefore, application of josamycin to the lesional skin of AD patients may provide relief from chronic inflammation mediated by mast cells.