Neutrophil protection against S. aureus progression Flashcards
(17 cards)
Q: What is infective endocarditis (IE)?
A: IE is an infection characterized by an infected thrombus at the heart valves, often caused by bacteria such as Staphylococcus aureus.
Q: What role do neutrophils play in infective endocarditis (IE)?
A: Neutrophils protect against IE by infiltrating the infected thrombi and surrounding vasculature, although their protective role is independent of NET release.
Q: What are neutrophil extracellular traps (NETs)?
A: NETs are extracellular DNA strands released by neutrophils that contain histones, granule proteins, and cytosolic proteins to trap and kill pathogens.
Q: How was the role of NETs in IE studied in the article?
A: The study used a murine model of Staphylococcus aureus endocarditis with immunostaining to identify NETs, neutrophil depletion, and neutrophil-selective PAD4-knockout mice.
Q: What was the effect of neutrophil depletion on the occurrence of IE?
A: Neutrophil depletion increased the occurrence of IE.
Q: What are staphylocoagulases, and what role do they play in IE?
A: Staphylocoagulases (coagulase and von Willebrand factor binding protein) induce fibrin formation and contribute to IE severity by preventing NETs from constraining infection and causing tissue damage.
Q: What was the effect of the absence of staphylocoagulases on IE?
A: Absence of staphylocoagulases led to improved survival, decreased bacteremia, smaller infiltrates, and decreased tissue destruction in IE.
Q: How does S. aureus manipulate the coagulation cascade and immune system in IE?
A: S. aureus uses virulence factors like staphylocoagulases to induce fibrin formation, shielding bacteria from immune cells, and evades neutrophil and NET defenses.
Q: What is the significance of PAD4 in the context of NET formation?
A: PAD4 (peptidylarginine deiminase 4) is an enzyme crucial for NET formation; PAD4-deficient mice show substantially reduced NET release.
Q: What are the key findings regarding NETs in inflammation-induced endocarditis?
A: Neutrophils protect against IE independently of NET release, and the absence of S. aureus staphylocoagulases reduces IE severity and increases NET levels.
Q: How effective are NETs against S. aureus–induced endocarditis?
A: NETs are largely ineffective due to neutrophil entry into thrombi being shielded by fibrin produced by S. aureus.
Q: What was observed in neutrophil-depleted mice?
A: Increased occurrence of endocarditis and persistent bacteremia, indicating neutrophils minimize disease progression.
Q: How do S. aureus USA300 and other strains influence NET release?
A: They induce dense areas of NETs and NET-releasing neutrophils in mice, showing high potency in NET induction.
Q: How does S. aureus evade neutrophil defense mechanisms?
A: Through the production of staphylocoagulases, which form a protective fibrin layer around the thrombus, shielding bacteria from neutrophils.
Q: What effect does deleting staphylocoagulases have on endocarditis?
A: It prevents leukocyte infiltrate accumulation, reduces tissue apoptosis, and improves survival rates and bacteremia levels in infected mice.
Q: What is the significance of extracellular DNA in the context of endocarditis?
A: Extracellular DNA, potentially not of NET origin, contributes to vegetation formation and can be degraded by DNases, improving endocarditis outcomes.
Q: What therapeutic strategies might improve outcomes in S. aureus–induced endocarditis?
A: Combining antibiotics with treatments targeting staphylocoagulases or enhancing NET efficacy might reduce vegetation size and bacterial load.
