Endocarditis Pathogen Promotes Vegetation Formation by Inducing Intravascular Neutrophil Extracellular Traps Through Activated Platelets

Jung, Chiau Jing; Yeh, Chiou Yueh; Hsu, Ron Bin; Lee, Chi-Ming; Shun, Chia‐Tung; Chia, Jean-San

doi:10.1161/circulationaha.114.011432

Cited by 73 publications

(95 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In fact, CBP-negative strains have been isolated from the blood of IE patients (49). Thus, CBP-negative S. mutans strains are also related to virulence in IE (56,58,59), though the intensity of the pathogenicity and the mechanisms of IE development appear to be different from those for CBP-positive S. mutans strains.…”

Section: Discussionmentioning

confidence: 99%

Contribution of Streptococcus mutans Strains with Collagen-Binding Proteins in the Presence of Serum to the Pathogenesis of Infective Endocarditis

et al. 2017

View full text Add to dashboard Cite

Streptococcus mutans, a major pathogen of dental caries, is considered one of the causative agents of infective endocarditis (IE). Recently, bacterial DNA encoding 120-kDa cell surface collagen-binding proteins (CBPs) has frequently been detected from S. mutans-positive IE patients. In addition, some of the CBP-positive S. mutans strains lacked a 190-kDa protein antigen (PA), whose absence strengthened the adhesion to and invasion of endothelial cells. The interaction between pathogenic bacteria and serum or plasma is considered an important virulence factor in developing systemic diseases; thus, we decided to analyze the pathogenesis of IE induced by S. mutans strains with different patterns of CBP and PA expression by focusing on the interaction with serum or plasma. CBP-positive (CBP ϩ )/PA-negative (PA Ϫ ) strains showed prominent aggregation in the presence of human serum or plasma, which was significantly greater than that with CBP ϩ /PA-positive (PA ϩ ) and CBP-negative (CBP Ϫ )/PAϩ strains. Aggregation of CBP ϩ /PA Ϫ strains was also observed in the presence of a high concentration of type IV collagen, a major extracellular matrix protein in serum. In addition, aggregation of CBP ϩ /PA Ϫ strains was drastically reduced when serum complement was inactivated. Furthermore, an ex vivo adherence model and an in vivo rat model of IE showed that extirpated heart valves infected with CBP ϩ /PA Ϫ strains displayed prominent bacterial mass formation, which was not observed following infection with CBP ϩ /PA ϩ and CBP Ϫ /PA ϩ strains. These results suggest that CBP ϩ /PA Ϫ S. mutans strains utilize serum to contribute to their pathogenicity in IE. KEYWORDS Streptococcus mutans, blood, infective endocarditisG ram-positive cocci, such as Staphylococcus aureus and viridans group streptococci, are major pathogens in infective endocarditis (IE) (1, 2). One of the important steps for the pathogenesis of IE is invasion of pathogenic bacteria into the bloodstream (1). Viridans group streptococci invade the bloodstream following professional dental treatment as well as routine daily oral care (3, 4) and are associated with a risk for IE in subjects with underlying heart disorders, though these bacteria are predominantly phagocytosed and eliminated in healthy humans (5).Streptococcus mutans, classified as a viridans group streptococcus, is a major pathogen of dental caries and is occasionally isolated from the blood of IE patients (6). In 1993, approximately 10 to 20% of S. mutans strains were demonstrated to possess collagen-binding activity, which was regarded to be advantageous for binding to collagenous tissue, such as dentin (7). Thereafter, 120-kDa collagen-binding proteins (CBPs), which were classified as Cnm and Cbm, were identified on the cell surfaces of some S. mutans strains in 2004 and 2012, respectively (8, 9).

show abstract

Section: Discussionmentioning

confidence: 99%

Contribution of Streptococcus mutans Strains with Collagen-Binding Proteins in the Presence of Serum to the Pathogenesis of Infective Endocarditis

et al. 2017

View full text Add to dashboard Cite

show abstract

“…NETs adhere to various pathogens in vivo, and may facilitate killing of organisms that are too large to be ingested [9], but it has been postulated that this attachment may be utilised by certain organisms to form biofilms, and may induce direct tissue damage [10]. There is also conflicting evidence for a direct microbicidal effect of NETs [8,11].…”

Section: Principal Effector Functions Of Neutrophilsmentioning

confidence: 99%

Hypoxic regulation of neutrophil function and consequences for Staphylococcus aureus infection

Lodge

Thompson

Chilvers

et al. 2017

Microbes and Infection

View full text Add to dashboard Cite

show abstract

“…In a model of endocarditis, cultured bacteria from endocarditis patients were infused through carotid catheters into rats (63). By confocal microscopy, a platelet/bacteria layer was demonstrated inside the vegetation film, which was also intermixed with NETs (63).…”

Section: Platelets and Netosismentioning

confidence: 99%

“…By confocal microscopy, a platelet/bacteria layer was demonstrated inside the vegetation film, which was also intermixed with NETs (63). Furthermore, deoxyribonuclease (DNase, an enzyme that degrades DNA) proved to be an effective treatment (63). Platelets were deemed necessary for NETosis in this model, shown by inhibition with aspirin (63).…”

Section: Platelets and Netosismentioning

confidence: 99%

Intercellular Interactions as Regulators of NETosis

2016

View full text Add to dashboard Cite

Neutrophil extracellular traps (NETs) are chromatin-derived webs extruded from neutrophils in response to either infection or sterile stimulation with chemicals, cytokines, or microbial products. The vast majority of studies have characterized NET release (also called NETosis) in pure neutrophil cultures in vitro. The situation is surely more complex in vivo as neutrophils constantly sample not only pathogens and soluble mediators but also signals from cellular partners, including platelets and endothelial cells. This complexity is beginning to be explored by studies utilizing in vitro co-culture, as well as animal models of sepsis, infective endocarditis, lung injury, and thrombosis. Indeed, various selectins, integrins, and surface glycoproteins have been implicated in platelet–neutrophil interactions that promote NETosis, albeit with disparate results across studies. NETosis can also clearly be regulated by soluble mediators derived from platelets, such as eicosanoids, chemokines, and alarmins. Beyond platelets, the role of the endothelium in modulating NETosis is being increasingly revealed, with adhesive interactions likely priming neutrophils toward NETosis. The fact that the same selectins and surface glycoproteins may be expressed by both platelets and endothelial cells complicates the interpretation of in vivo data. In summary, we suggest in this review that the engagement of neutrophils with activated cellular partners provides an important in vivo signal or “hit” toward NETosis. Studies should, therefore, increasingly consider the triumvirate of neutrophils, platelets, and the endothelium when exploring NETosis, especially in disease states.

show abstract

Endocarditis Pathogen Promotes Vegetation Formation by Inducing Intravascular Neutrophil Extracellular Traps Through Activated Platelets

Cited by 73 publications

References 50 publications

Contribution of Streptococcus mutans Strains with Collagen-Binding Proteins in the Presence of Serum to the Pathogenesis of Infective Endocarditis

Contribution of Streptococcus mutans Strains with Collagen-Binding Proteins in the Presence of Serum to the Pathogenesis of Infective Endocarditis

Hypoxic regulation of neutrophil function and consequences for Staphylococcus aureus infection

Intercellular Interactions as Regulators of NETosis

Contact Info

Product

Resources

About