Interferon‐ γ enhances both the anti‐bacterial and the pro‐inflammatory response of human mast cells to Staphylococcus aureus

Summary Human mast cells (hu MC s) are involved in both innate and adaptive immune responses where they release mediators including amines, reactive oxygen species ( ROS ), eicosanoids and cytokines. We have reported that interferon‐ γ ( IFN ‐ γ ) enhances Fc γ R‐dependent ROS production. The aim of this study was to extend these observations by investigating the effect of IFN ‐ γ on the biological responses of hu MC s to Staphylococcus aureus . We found that exposure of hu MC s to S. aureus generated intracellular and extracellular ROS , which were enhanced in the presence of IFN ‐ γ . IFN ‐ γ also promoted bacteria killing, β ‐hexosaminidase release and eicosanoid production. Interferon‐ γ similarly increased expression of mRNA s encoding CCL 1 to CCL 4, granulocyte–macrophage colony‐stimulating factor ( GM ‐ CSF ), tumour necrosis factor‐ α and CXCL 8 in S. aureus ‐stimulated hu MC s. The ability of IFN ‐ γ to increase CXCL 8 and GM ‐ CSF protein levels was confirmed by ELISA . Fibronectin or a β 1 integrin blocking antibody completely abrogated IFN ‐ γ ‐dependent S. aureus binding and reduced S. aureus ‐dependent CXCL 8 secretion. These data demonstrate that IFN ‐ γ primes hu MC s for enhanced anti‐bacterial and pro‐inflammatory responses to S. aureus , partially mediated by β 1 integrin.