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Thromb Haemost 2019; 119(05): 786-796
DOI: 10.1055/s-0039-1678665
Blood Cells, Inflammation and Infection
Georg Thieme Verlag KG Stuttgart · New York

Neutrophil Extracellular Traps Enhance Staphylococcus Aureus Vegetation Formation through Interaction with Platelets in Infective Endocarditis

Chih-Chieh Hsu
1   Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
,
Ron-Bin Hsu
2   Division of Cardiovascular Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
,
Ryosuke L. Ohniwa
3   Division of Biomedical Science, Faculty of Medicine, University of Tsukuba Tennoh-dai, Tsukuba, Ibaraki, Japan
4   Center of Biotechnology, National Taiwan University, Taipei, Taiwan
,
Jeng-Wei Chen
5   Division of Cardiovascular Surgery, Department of Surgery, National Taiwan University Hospital Hsin Chu branch, Hsin Chu, Taiwan
6   Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Chang-Tsu Yuan
7   Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
,
Jean-San Chia
8   Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Chiau-Jing Jung 
9   Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
› Author Affiliations Funding This work was supported by the Ministry of Science and Technology (MOST; grants 106–2320-B-002 -022 -MY3, and 106–2320-B-038 -004 -MY2).
Further Information

Publication History

10 August 2018

31 December 2018

Publication Date:
07 February 2019 (online)

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Abstract

The mechanisms or host factors involved in septic thrombus or vegetation formation in Staphylococcus aureus-induced infective endocarditis (IE) are unclear. Using an experimental endocarditis rat model, here we demonstrated that S. aureus HG001-induced vegetation was composed of bacterial floes encased in aggregated platelets and surrounded by neutrophil extracellular traps (NETs). In vitro data demonstrated that platelets contribute to both biofilm and NET formation. Prophylactic administration of DNase I significantly reduced the size of vegetation induced by methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains, even though MRSA and MSSA isolates express different biofilm phenotypes and NET-induction abilities in the presence of platelets. Moreover, delivery of both DNase I and daptomycin prophylactically and therapeutically produced synergistic effects by reducing vegetation size and bacterial numbers on damaged valve tissues in MRSA-induced IE. Together, these data suggest that NETs contribute to vegetation formation in S. aureus endocarditis and DNase I has the potential to control S. aureus-induced IE in the clinic.

Keywords

infective endocarditis - staphylococcus aureus - neutrophil extracellular traps - platelets - DNase I

Supplementary Material

 

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