NETs Enhance Macrophage Antibacterial Activity

According to Vanderbilt University researchers, neutrophil extracellular traps (NETs) boost the bacterial killing power of macrophages. 

“Neutrophils produce the spider webs that immobilize the bacteria, and macrophages are the spiders that engulf and kill the bacteria,” said Eric Skaar, senior author of the paper published in Science Advances today. 

Neutrophils and macrophages are both phagocytic cells known for ingesting bacteria and producing antimicrobial peptides, reactive oxygen species and other enzymes to fight infection. NET generation (NETosis), thought to be a form of programmed cell death, is a more recently discovered neutrophil antibacterial strategy, Skaar said. The released neutrophil DNA creates a sticky trap that is also studded with antimicrobial peptides. 

First author Andrew Monteith and colleagues used neutrophils that undergo increased NETosis in animal and in vitro model systems to study the biological function of NETs. They found that increased NETosis did not provide a killing advantage to neutrophils in isolation. But when macrophages were present, NET formation enhanced macrophage antibacterial activity by increasing phagocytosis —of staph bacteria stuck in the NETs along with neutrophil antimicrobial peptides. 

“The macrophages end up with not only their own antibacterial arsenal, but also the neutrophils’ antibacterial arsenal, all in the same compartment killing the bacteria,” Skaar said. 

Increased NETosis also boosted macrophage killing of other bacterial pathogens including Streptococcus pneumoniae and Pseudomonas aeruginosa. The findings suggest that neutrophil/NET-macrophage cooperation is a broadly used immune defense mechanism.