Data for main and supplementary figures

<i>Staphylococcus aureus</i> is a major pathogen responsible for a wide range of infections, from minor skin diseases to life-threatening conditions, such as sepsis and pneumonia. Its ability to invade nonphagocytic cells, evading the immune system and persisting intracellularly complicates the treatment and contributes to recurrent infections. In this study, we investigated the role of cytokines in inhibiting <i>S. aureus</i> adherence and invasion into nonphagocytic human cells. Monomac-6 cells were stimulated with heat-killed <i>S. aureus</i> (HKSA) to produce a cytokine cocktail, which was used to treat various human cell lines, including HEK293, A549, HaCaT, and HT29. Our results demonstrate that cytokines significantly reduced <i>S. aureus</i> adherence and invasion into HEK293, HaCaT, and HT29 cells by altering the expression of key host cell receptors for <i>S. aureus </i>adhesins and invasion, such as integrins and heat shock proteins. These effects of cytokines were mediated via JAK-STAT pathway as tofacitinib supplementation, a JAK inhibitor, reversed the effects of cytokine cocktail. However, these effects were not observed in A549 cells, most likely due to their ability to actively internalize pathogens. These findings suggest that cytokines provide a crucial line of defense against the ability of <i>S. aureus</i> to invade nonphagocytic cells by modulating the expression of host cells receptors.金黄色葡萄球菌（Staphylococcus aureus）是一类引发多种感染的主要致病菌，感染范围涵盖轻微皮肤疾病至脓毒症、肺炎等致命病症。其具备侵袭非吞噬细胞、逃避免疫系统并在胞内持续定植的能力，这一特性不仅加大了临床治疗难度，还会增加感染复发的风险。本研究聚焦于细胞因子在抑制金黄色葡萄球菌黏附并侵袭人类非吞噬细胞过程中的作用机制。研究人员采用热灭活金黄色葡萄球菌（HKSA）刺激Monomac-6细胞，以诱导其分泌细胞因子混合物，随后利用该混合物处理HEK293、A549、HaCaT及HT29等多株人类细胞系。实验结果表明，通过调控金黄色葡萄球菌黏附素与侵袭相关的关键宿主细胞受体（如整合素与热休克蛋白）的表达水平，细胞因子可显著降低金黄色葡萄球菌在HEK293、HaCaT及HT29细胞中的黏附与侵袭效率。进一步实验证实，细胞因子的上述调控作用经由JAK-STAT信号通路（JAK-STAT pathway）介导：添加JAK抑制剂托法替布（tofacitinib）可逆转细胞因子混合物所产生的效应。但该保护效应在A549细胞中未被观测到，这大概率源于A549细胞具备主动摄取病原体的能力。综上，本研究结果提示，细胞因子可通过调控宿主细胞受体的表达，为抵御金黄色葡萄球菌侵袭非吞噬细胞提供一道关键的免疫防御屏障。