The important human pathogen Staphylococcus aureus displays a dazzling array of strategies for evading the immune system. In Science, Schneewind and colleagues demonstrate that S. aureus is also able to subvert neutrophil extracellular traps (NETs) to kill host macrophages. Neutrophils release NETs (tangles of nucleic acid interspersed with antimicrobial peptides) in response to bacteria, and this represents an important protective mechanism. Also important are macrophages, which phagocytose bacteria; however, the characteristic abcess of S. aureus almost completely lacks macrophages. S. aureus expresses two virulence factors, a nuclease and an adenosine synthase, which process NET DNA into cytotoxic 2′-deoxyadenosine. In the absence of antimicrobial peptides, 2′-deoxyadenosine alone is sufficient to trigger an intrinsic apoptosis pathway in macrophages but not in neutrophils. S. aureus is thus able to redirect an otherwise functional host antibacterial mechanism to destroy protective macrophages.

Science 342, 863–866 (2013)