The University of Southampton
University of Southampton Institutional Repository

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

Interferon-gamma enhances both the anti-bacterial and the pro-inflammatory response of human mast cells to Staphylococcus aureus
Interferon-gamma 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-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.
0019-2805
470-485
Swindle, Emily
fe393c7a-a513-4de4-b02e-27369bd7e84f
Brown, Jared
d0af823c-869f-44f0-b946-a9ff10403c2b
Radinger, Madeleine
b270b886-47c3-4157-a2c5-8ebe06f3f645
DeLeo, Frank
a2d6094a-c6d6-476b-aaac-3c6a638cac3d
Metcalfe, Dean
c27113f8-8f16-4612-822e-2cfbcf3643c4
Swindle, Emily
fe393c7a-a513-4de4-b02e-27369bd7e84f
Brown, Jared
d0af823c-869f-44f0-b946-a9ff10403c2b
Radinger, Madeleine
b270b886-47c3-4157-a2c5-8ebe06f3f645
DeLeo, Frank
a2d6094a-c6d6-476b-aaac-3c6a638cac3d
Metcalfe, Dean
c27113f8-8f16-4612-822e-2cfbcf3643c4

Swindle, Emily, Brown, Jared and Radinger, Madeleine et al. (2015) Interferon-gamma enhances both the anti-bacterial and the pro-inflammatory response of human mast cells to Staphylococcus aureus. Immunology, 146 (3), 470-485. (doi:10.1111/imm.12524). (PMID:26288256)

Record type: Article

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.

PDF
Swindle et al 2015_Immunology open access version.pdf - Accepted Manuscript
Download (2MB)

More information

Accepted/In Press date: 12 August 2015
e-pub ahead of print date: 19 August 2015
Published date: 1 November 2015
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 396184
URI: https://eprints.soton.ac.uk/id/eprint/396184
ISSN: 0019-2805
PURE UUID: 9f56d651-8d65-4e58-b130-230c1669e59e
ORCID for Emily Swindle: ORCID iD orcid.org/0000-0003-3644-7747

Catalogue record

Date deposited: 07 Jun 2016 10:47
Last modified: 10 Jan 2019 01:33

Export record

Altmetrics

Contributors

Author: Emily Swindle ORCID iD
Author: Jared Brown
Author: Madeleine Radinger
Author: Frank DeLeo
Author: Dean Metcalfe

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×