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When faced with threats ranging from snake bites to COVID infections, some white blood cells retaliate with a peculiar tactic: spewing out their own DNA to form pathogen-trapping nets. But research suggests that sometimes this web-deploying response might do our bodies more harm than good.

Hosted by: Stefan Chin

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[♪ INTRO].

Like all mammals, we humans rely on our immune systems to protect us from all sorts of dangers. Much of that defense is shouldered by white blood cells called neutrophils.

They account for 50 to 80 percent of your circulating white blood cells. And when they encounter a problem, they do what you’d expect white blood cells to do: engulf, dissolve and eliminate. But in 2004, we discovered these little cells can do something more drastic: they can explode into a gooey net.

Now, this process is still a bit mysterious, but it seems to be an ancient, foundational action of our immune system. It shows up in everything from COVID-19 to venomous snakebites. And understanding how to stop it from happening might be the key to saving lives from both.

Neutrophils are essentially your immune system’s first responders. They’re quick to show up at the site of an infection or injury and start setting things right. And their most well-known response to a problem— like an invading bacterium— is to, essentially, swallow and destroy it via a process called phagocytosis.

But sometimes, they go for a nuclear option. They send out webs of sticky material called neutrophil extracellular traps, or NETs for short. The remarkable thing is that these NETs seem to be made of the cells’ own DNA.

When this option is triggered, internal chemical pathways lead to the unwinding of the cell’s DNA-containing chromatin, which eventually explodes out in a web. This usually takes a few hours, and it results in the cell’s death— so it’s referred to as NETosis, to line up with the terminology for other kinds of cell death, like necrosis. There also seems to be a faster, though not-quite-as-well documented version that doesn’t kill the cell.

All or part of the cell’s DNA is ejected in a NET, but without the dramatic explosion. And somehow, this lets the cell continue to prowl around and eat things. Kind of like a zombie, if zombies attacked by throwing their brains at you.

But either way, these NETs live up to their names: they trap invading pathogens. And their chromatin “ropes” seem to be covered in antimicrobial compounds. So they trap and kill.

We’ve studied them quite a bit with bacteria. Though, they’re also triggered by viruses, fungi, and some parasites. Even the venom from snakebites can cause them to form, as well as just regular old cuts and injuries.

And that may be because NETs help our bodies jump-start blood clotting and inflammation, which can help wounds heal. So overall, NETs seem like a wonderful, vital part of keeping us healthy. But nothing in the immune system is ever this easy.

For starters, NETosis is not a sure-fire method. Pathogens may have ways around NETs. Like, the HIV-1 virus can inhibit their formation, and streptococcal bacteria can digest them.

Some bacteria may even hide from the rest of the immune system inside NETs. Which kinda defeats the purpose. And the more we’ve looked into this process, the more we’ve realized that NETosis is— as some studies have put it— a double-edged sword.

Take snakebites, for instance. The NETs and the blood clots they cause might help contain venom toxins to a particular area, keeping the damage localized. But this comes at a huge cost.

It can effectively doom that body part. And since the dying tissue can, in turn, doom the whole person if it’s not removed, that’s not great. But perhaps more simply: creating little sticky masses in your blood vessels can be a bit of a problem at times, especially if there are more of them than the body can clear, or they outlast their welcome.

Basically, NETs can cause clotting problems —which means they can complicate other diseases and infections, as well. For example, a 2011 study suggests that, in their efforts to combat flu infections,. NETs can end up damaging the tiny air sacs and blood vessels in the lungs.

Oh, and they may be involved in COVID-19! Clotting problems do seem to happen fairly often in the disease, and a small study which compared 33 COVID-19 patients to 17 uninfected people found evidence for NET-containing clots in the lungs. In fact, their formation was positively correlated with case severity!

NETosis is also tied to a number of auto-immune and inflammatory conditions. Which could be because, when the cells explode, they also release signaling molecules that rile up the immune system. Plus, the NETs themselves can damage nearby healthy cells.

But this might be good news, since it means NETosis might be a good target for designing new treatments. Studying how the body goes wrong is often one of the best ways to discover how to heal people. For instance, for snakebites, it’s been suggested that giving NET-digesting enzymes alongside antivenoms might reduce tissue damage.

Basically, it could let the toxins escape the body’s traps— right into the arms of the antivenom proteins that inhibit them. And if NETosis is contributing to symptom severity in certain infections, then reducing NETosis might alleviate the worst symptoms. So it might help reduce the harm from viral diseases like COVID.

But ultimately, NETs remind us that our immune systems are incredibly complicated. While they’ve evolved to keep us safe, some pathogens have adapted to counteract or even take advantage of them. And at other times, a normally beneficial system goes overboard and ends up threatening the safety of the whole body.

So by studying the immune system and the components of it like NETs, we can appreciate the complex machine evolution has given us— while also discovering ways to tune-up that machine when it starts acting a little funny. Thank you for watching this episode of SciShow! And before I go, I wanted to remind you that it’s almost the end of July— which means time is running out to get this month’s SciShow pin!

This month’s design features Deep Impact, which crashed an impactor into the comet Tempel 1 so that we could learn more about what comets are made of. And you can learn all about it in our SciShow Space episode about that mission! But this stylish homage is only available until July 31st— so be sure to order yours soon!

You can find it in the merch shelf below the video, or by searching for “SciShow Pin of the Month” at DFTBA.com. [♪ OUTRO].