Editors' ChoiceImmunology

Neutrophil Superheroes: Casting NETs to Catch Bacteria

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Science Translational Medicine  12 Sep 2012:
Vol. 4, Issue 151, pp. 151ec163
DOI: 10.1126/scitranslmed.3004900

Neutrophils are the unsung heroes of the immune system, always on the front line of defense against infection. These noble cells were thought to battle to the death: During pathogen-induced cell death, neutrophils release extracellular traps (NETs) that can capture bacterial, fungal, and parasitic pathogens in a process termed NETosis. Now, Yipp et al. report that neutrophils may have some of the resiliency of superheroes as well. They found that early in infection, neutrophils undergoing NETosis don’t just roll over and die, but continue to crawl—casting wide areas of NETs that further prevent the spread of infection.

The authors used intravital microscopy in mice to study the in vivo dynamics of neutrophils during skin infection with Staphylococcus aureus and Streptococcus pyogenes, two Gram-positive bacteria that frequently cause infection in human patients. Using a dye that stains for DNA, the authors observed neutrophils extruding large sheets of DNA while simultaneously crawling toward bacteria. NETosis was regulated by innate immune signaling through Toll-like receptor 2 (TLR2), which binds a bacterial cell wall component, and complement pathway protein C3, which coats and helps neutralize bacteria. NETs appeared to limit the extent of staph infection in vivo, whereas C3-deficient and TLR2-deficient mice had difficulty containing the spread of bacteria from the original site of infection and an increased risk of bacteremia. Human neutrophils behaved similarly in mouse skin and in samples from human abscesses contained NETosing neutrophils, suggesting that these studies may directly apply to human biology.

Future work may reveal ways to support the neutrophils in their fight against infection by NETosis or to decrease NETosis in situations that may damage human tissue, such as in autoimmune vasculitis. In the meantime, we can thank our microscopic superheroes, who crawl while defending the body from invasion by sacrificing their own DNA.

B. G. Yipp et al., Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat. Med., published online 26 August 2012 (10.1038/nm.2847). [Abstract]

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