Staphylococcal SSL5-induced platelet microparticles provoke proinflammatory responses via the CD40/TRAF6/NFKB signalling pathway in monocytes

Jun-Jie Bei; Chuan Liu; Song Peng; Cheng-Hai Liu; Wei-Bo Zhao; Xiao-Long Qu; Qiang Chen; Zhou Zhou; Zheng-Ping Yu; Karlheinz Peter; Hou-Yuan Hu

doi:10.1160/th15-04-0322

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2016; 115(03): 632-645
DOI: 10.1160/th15-04-0322

Blood Cells, Inflammation and Infection

Schattauer GmbH

Staphylococcal SSL5-induced platelet microparticles provoke proinflammatory responses via the CD40/TRAF6/NFKB signalling pathway in monocytes

Jun-Jie Bei

¹Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China

³Department of Cardiology, Guangxi Provincial Corps Hospital of CAPF, Nanning, Guangxi, China

,

Chuan Liu

²Department of Occupational Health, Faculty of Preventive Medicine, Third Military Medical University, Chongqing, China

,

Song Peng

¹Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China

,

Cheng-Hai Liu

¹Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China

,

Wei-Bo Zhao

¹Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China

,

Xiao-Long Qu

¹Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China

,

Qiang Chen

¹Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China

,

Zhou Zhou

²Department of Occupational Health, Faculty of Preventive Medicine, Third Military Medical University, Chongqing, China

,

Zheng-Ping Yu

²Department of Occupational Health, Faculty of Preventive Medicine, Third Military Medical University, Chongqing, China

,

Karlheinz Peter

⁴Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, and Department of Medicine and Immunology, Monash University, Melbourne, Victoria, Australia

,

Hou-Yuan Hu

¹Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China

› Author Affiliations

Abstract

Summary

Pathogens-induced platelet activation contributes to inflammation in cardiovascular diseases, but underlying mechanisms remain elusive. Staphylococcal superantigen-like protein 5 (SSL5) is a known activator of platelets. Here we examined whether SSL5 is implicated in Staphylococcus aureus (S. aureus)-induced inflammation and potential mechanisms involved. As expected, we show that SSL5 activates human platelets and induces generation of platelet microparticles (PMPs). Flow cytometry and scanning electron microscopy studies demonstrate that SSL5-induced PMPs (SSL5-PMPs) bind to monocytes, causing aggregate formation. In addition, SSL5-PMPs provoke monocyte expression and release of inflammatory mediators, including interleukin-1β (IL-1β), tumour necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in a dose- and time-dependent manner. SSL5-PMPs also enhance MCP-1-induced monocyte migration. Blockade of CD40 and CD40 ligand (CD40L) interactions with neutralising antibodies significantly reduce monocyte release of inflammatory mediators and migration induced by SSL5-PMPs. SiRNA-mediated silencing of CD40 or TNF receptor (TNFR)-associated factor 6 (TRAF6) gene largely abrogates phosphorylation and nuclear translocation of NFkB (p65). In conclusion, SSL5 provokes the release of inflammatory mediators in monocytes, at least in part, via PMPs-mediated activation of the CD40/TRAF6/NFkB signalling pathway, though it normally inhibits leukocyte function. Our findings thus reveal a novel mechanism by which S. aureus induces inflammation.

Keywords

Staphylococcal superantigen-like protein 5 - platelet microparticles - monocytes - inflammation - CD40 ligand

Full Text

References

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