Perforin-2 (P-2) is an antimicrobial protein with unique properties to kill intracellular bacteria. Gamma delta (GD) T cells, as the major T cell population in epithelial tissues, play a central role in protective and pathogenic immune responses in the skin. However, the tissue-specific mechanisms that control the innate immune response and the effector functions of GD T cells, especially the cross-talk with commensal organisms, are not very well understood. We hypothesized that the most prevalent skin commensal microorganism, Staphylococcus epidermidis, may play a role in regulating GD T cell-mediated cutaneous responses. We analyzed antimicrobial protein P-2 expression in human skin at a single cell resolution using an amplified fluorescence in situ hybridization approach to detect P-2 mRNA in combination with immunophenotyping. We show that S. epidermidis activates GD T cells and upregulates P-2 in human skin ex vivo in a cell-specific manner. Furthermore, P-2 upregulation following S. epidermidis stimulation correlates with increased ability of skin cells to kill intracellular Staphylococcus aureus. Our findings are the first to reveal that skin commensal bacteria induce P-2 expression, which may be utilized beneficially to modulate host innate immune responses and protect from skin infections.

Perforin-2 (P-2) 是一种抗菌蛋白，具有杀死细胞内细菌的独特特性。Gamma delta (GD) T 细胞作为上皮组织中的主要 T 细胞群，在皮肤的保护性和致病性免疫反应中发挥着核心作用。然而，控制先天免疫反应和 GD T 细胞效应功能的组织特异性机制，尤其是与共生生物的串扰，还不是很清楚。我们假设最普遍的皮肤共生微生物，表皮葡萄球菌, 可能在调节 GD T 细胞介导的皮肤反应中发挥作用。我们使用放大的荧光以单细胞分辨率分析了人类皮肤中抗微生物蛋白 P-2 的表达就地结合免疫表型检测 P-2 mRNA 的杂交方法。我们证明表皮葡萄球菌 激活 GD T 细胞并上调人体皮肤中的 P-2 离体以特定于细胞的方式。此外，P-2 上调后表皮葡萄球菌 刺激与皮肤细胞杀死细胞内的能力增加有关 金黄色葡萄球菌. 我们的研究结果首次揭示了皮肤共生细菌诱导 P-2 表达，这可能有助于调节宿主先天免疫反应并防止皮肤感染。