Interferon-γ enhances both the anti-bacterial and the pro-inflammatory response of human mast cells to Staphylococcus aureus.
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-γ (IFN-γ) enhances FcγR-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 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-γ. IFN-γ also promoted bacteria killing, β-hexosaminidase release and eicosanoid production. Interferon-γ similarly increased expression of mRNAs encoding CCL1 to CCL4, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-α and CXCL8 in S. aureus-stimulated huMCs. The ability of IFN-γ to increase CXCL8 and GM-CSF protein levels was confirmed by ELISA. Fibronectin or a β1 integrin blocking antibody completely abrogated IFN-γ-dependent S. aureus binding and reduced S. aureus-dependent CXCL8 secretion. These data demonstrate that IFN-γ primes huMCs for enhanced anti-bacterial and pro-inflammatory responses to S. aureus, partially mediated by β1 integrin.
Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK.
Emily J
EJ
Swindle
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Jared M
JM
Brown
Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Göteborg, Sweden.
Madeleine
M
Rådinger
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MA, USA.
Frank R
FR
DeLeo
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Dean D
DD
Metcalfe
D056704:Adaptive Immunity; D000818:Animals; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
C508606:CXCL8 protein, human; D019742:Chemokines, CC; D016207:Cytokines; D018836:Inflammation Mediators; D019012:Integrin beta1; D016209:Interleukin-8; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
bacteria; innate immunity; interferon-γ; mast cells; β1 integrin