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

Abstract

Human mast cells (huMCs) 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-gamma (IFN-gamma) enhances FcgammaR-dependent ROS production. The aim of this study was to extend these observations by investigating the effect of IFN-gamma on the biological responses of huMCs to Staphylococcus aureus. We found that exposure of huMCs to S. aureus generated intracellular and extracellular ROS, which were enhanced in the presence of IFN-gamma. IFN-gamma also promoted bacteria killing, beta-hexosaminidase release and eicosanoid production. Interferon-gamma similarly increased expression of mRNAs encoding CCL1 to CCL4, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha and CXCL8 in S. aureus-stimulated huMCs. The ability of IFN-gamma to increase CXCL8 and GM-CSF protein levels was confirmed by ELISA. Fibronectin or a beta1 integrin blocking antibody completely abrogated IFN-gamma-dependent S. aureus binding and reduced S. aureus-dependent CXCL8 secretion. These data demonstrate that IFN-gamma primes huMCs for enhanced anti-bacterial and pro-inflammatory responses to S. aureus, partially mediated by beta1 integrin.

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ORCID for Emily Swindle: orcid.org/0000-0003-3644-7747

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