"Spiderman, Spiderman, does whatever a Neutrophil (!!) can..."
Look out! Here comes the neutrophil.
I just saw the movie Spider-Man: Into the Spider-Verse last week, so the theme song is still stuck in my head. Fantastic movie by the way, highly recommend!
Today I will write about the neutrophil and how neutrophils, just like Spider-Man, can shoot webs of DNA to trap pathogens! These webs are called Neutrophil Extracellular Traps, or NETs.
Neutrophils are fascinating immune cells. They are the cells mainly responsible for killing bacteria and fighting infection.
Neutrophils can kill bacteria in several ways – they can engulf or ‘eat’ bacteria by a process called phagocytosis, and then they can kill the bacteria using toxic chemicals like bleach and hydrogen peroxide. Neutrophils can release potent antimicrobial molecules that can also kill bacteria. Recently, in 2004, the NET was discovered.
So what are NETs?
Imagine you are a neutrophil for a second and you encounter a bacterium at arms reach (so not quite close enough to grab it and eat yourself). You would need something long and sticky to immobilize the bacteria in its place so then you can crawl up and eat it before it gets away. What’s something that is long and sticky in a cell? (Answer: DNA)
NETs are made up of long webs of DNA. In addition, the neutrophil adds some of its antimicrobial molecules to the NET so that the bacteria won’t be able to survive within the NET. The process of neutrophils making and releasing NETs is termed ‘NETosis’.
NETosis was thought to be a be-all end-all mechanism for the neutrophil, because once it spits out all of its DNA in theory the cell won’t be able to survive any longer. But in fact, my lab back in 2012 discovered that a neutrophil is still able to crawl around and be active for a while without its DNA.
NETosis, albeit effective at trapping and killing bacteria, poses some risks. DNA is damaging, and too much DNA left outside of the cell can cause unwanted inflammation. But, there are specific molecules (called DNases) that break up DNA to prevent this.
Interesting fact- some bacteria have evolved to make their own DNases which can break down NETs, which releases them from this fatal trap. I think this is very cool how bacteria can take advantage of these processes, and one of the many reasons why need to keep studying these interactions between bacteria and the immune system.
Another risk that NETs pose is the development of autoimmune diseases. If too many NETs are not cleaned up, one could develop antibodies against NETs and start an autoimmune response that can be detrimental. The buildup of NETs inside blood vessels also pose a risk for development of thrombosis or blood clots, and that’s why there are DNases present in the blood to prevent this.
Despite all the risks, your friendly neighborhood neutrophil has a pretty cool way to trap and kill bacteria in an effort to fight infections.
Discovery of NETs:
Brinkmann et al., 2004. Neutrophil extracellular traps kill bacteria. Science
NETs in vivo:
Yipp et al., 2012. Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nature Medicine.
NETs and blood clots:
Jimenez-Alcazar et al., 2017. Host DNases prevent vascular occlusion by neutrophil extracellular traps. Science.