Staphylococcus aureus Degrades Neutrophil Extracellular Traps to Promote Immune Cell Death

Vilasack Thammavongsa, Dominique M. Missiakas, Olaf Schneewind.

 Science. 2013 Nov 15;342(6160):863-6.

Speaker: Beatrice Lin (林怡慈)                                            Time: 13:10~14:00, Apr. 30, 2014

Commentator: Dr. Ching-Chuan Liu (劉清泉 教授)  Place: Room 601

Abstract

Staphylococcus aureus is an important human pathogen that causes skin and soft tissue abscesses. S. aureus infection can trigger infiltration of neutrophil and release of DNA to form neutrophil extracellular traps (NETs), thereby immobilizing the pathogen for subsequent clearance by immune cells such as example macrophages (1). However, S. aureus evades NETs by releasing viru­lence factors that enable it to persist and replicate in the lesions. Although the interaction between S. aureus and neutrophils has been well studied, its interaction with macrophages remained unknown. By performing immunohistochemical examination of abscesses in mice that were infected with wild-type S. aureus, the authors noticed that bacteria were largely sur­rounded by neutrophils, whereas macrophages only accumulated at the periphery of abscesses. The authors wanted to explore how S. aureus can cause macrophage clearance after escaping from NETs. By screening for virulence factors that affected abscess formation, they found that the nuc and adsA mutants caused less macrophage death, which suggested that S. aureus generates a toxic product from host NETs in a process that depends on staphylococcal nuclease (Nuc) (2) and adenosine synthase A (AdsA) (1). Mass spectrometry analysis of NET cleavage reactions identified the DNA metabolite 2’-deoxyadenosine (dAdo), which is responsible for the cytotoxic effect on macrophages. The authors also demonstrated that production of dAdo by AdsA is sufficient to induce apoptosis of macrophages via the activation of caspase-3. In conclusion, this study uncovered two new S. aureus virulence factors, Nuc and AdsA, that can convert NETs to dAdo, thus triggering caspase-3-mediated death of immune cells and inhibition of phagocytosis.55

References

1. Thammavongsa V, Kern JW, Missiakas DM, Schneewind O. Staphylococcus aureus synthesizes adenosine to escape host immune responses. J Exp Med. 2009; 206(11):2417-27.
2. Berends ET, Horswill AR, Haste NM, Monestier M, Nizet V, von Köckritz-Blickwede M. Nuclease expression by Staphylococcus aureus facilitates escape from neutrophil extracellular traps.J Innate Immun. 2010; 2(6):576-86.