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 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 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 <i>S. aureus</i> to invade nonphagocytic cells by modulating the expression host cells receptors.