Report

Staphylococcus aureus Degrades Neutrophil Extracellular Traps to Promote Immune Cell Death

Science  15 Nov 2013:
Vol. 342, Issue 6160, pp. 863-866
DOI: 10.1126/science.1242255

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Slipping the NET

One spectacular response to bacterial infection is the release of NETs (neutrophil extracellular traps) of DNA from polymorphonuclear leukocytes that immobilize the pathogens and prevent phagocytosis by macrophages. Staphylococcus aureus evades NETs by degrading the DNA into deoxyadenosine (dAdo). Thammavongsa et al. (p. 863) found that dAdo also promotes immune cell death, which appears to ensure the exclusion of macrophages from the center of abscesses within which the bacteria survive.

Abstract

Bacterial invasion of host tissues triggers polymorphonuclear leukocytes to release DNA [neutrophil extracellular traps (NETs)], thereby immobilizing microbes for subsequent clearance by innate defenses including macrophage phagocytosis. We report here that Staphylococcus aureus escapes these defenses by converting NETs to deoxyadenosine, which triggers the caspase-3–mediated death of immune cells. Conversion of NETs to deoxyadenosine requires two enzymes, nuclease and adenosine synthase, that are secreted by S. aureus and are necessary for the exclusion of macrophages from staphylococcal abscesses. Thus, the pathogenesis of S. aureus infections has evolved to anticipate host defenses and to repurpose them for the destruction of the immune system.

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