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Staphylococcus aureus 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 immune system and persisting intracellularly complicates the treatment and contributes to recurrent infections. In this study we investigated the role of cytokines in inhibiting S. aureus adherence and invasion into nonphagocytic human cells. Monomac-6 cells were stimulated with heat-killed S. aureus (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 S. aureus adherence and invasion into HEK293, HaCaT, and HT29 cells by altering the expression of key host cell receptors for S. aureus adhesins and invasion, such as integrins and heat shock proteins. These effects of cytokines were mediated via JAK-STAT pathway as the 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 S. aureus to invade nonphagocytic cells by modulating the expression host cells receptors.金黄色葡萄球菌（Staphylococcus aureus）是一类主要病原菌，可引发从轻症皮肤疾病到脓毒症、肺炎等危及生命的多种感染性疾病。其能够侵入非吞噬细胞、逃避免疫系统并在细胞内持续存活，这一特性增加了治疗难度，还会导致复发性感染。本研究探究了细胞因子在抑制金黄色葡萄球菌黏附并侵入非吞噬性人类细胞过程中发挥的作用。研究人员使用热灭活金黄色葡萄球菌（heat-killed S. aureus, HKSA）刺激Monomac-6细胞以制备细胞因子混合物，随后用该混合物处理包括HEK293、A549、HaCaT及HT29在内的多株人类细胞系。实验结果表明，细胞因子可通过调节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，显著降低金黄色葡萄球菌对HEK293、HaCaT及HT29细胞的黏附与侵袭能力。细胞因子的上述作用经由JAK-STAT信号通路介导：补充JAK抑制剂托法替布（tofacitinib）可逆转该细胞因子混合物的效应。但在A549细胞中未观察到此类效应，这大概率是因为A549细胞能够主动内化病原体。本研究结果提示，细胞因子可通过调节宿主细胞受体的表达，为抵御金黄色葡萄球菌侵入非吞噬细胞提供关键防御防线。