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Bats are amazing and not just because they're the only mammal that can fly! But they also carry a lot of diseases that are dangerous to humans, and while that is definitely not their fault, there is actually a lot we can learn from their unique immune systems.

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One fifth of all mammal species today are bats. And that's awesome, because they help us out in all sorts of ways.

Like, they pollinate a lot of plants, help regrow forests and control pests, and their poop is pretty excellent fertilizer. Plus, they're just really cool. Some of them can sense magnetic fields, or use sound to find their food—and, of course, there's the one thing they all have in common: they can truly fly.

They're the only mammals around capable of powered flight... without the help of machines. But they're also somewhat notorious for something else: being flying sacks of germs. You might have noticed that part, what with all the talk about zoonotic diseases that's been happening lately.

Those are diseases that are passed to humans from other animals. And while bats aren't to blame for everything, they have played a role in the transmission of at least 11 viruses —probably 12, counting SARS-CoV-2. These diseases aren't the bats' fault, of course.

If anything, they're ours. Research shows that disturbing animal habitats is usually what causes the transfer of a zoonotic disease to humans. Still, bats in particular do carry a lot of viruses.

And that's because they have unique immune systems. Which means we can learn a lot about these pathogens and their effects by studying bats. In fact, bat immune systems are so special that what we learn from them could someday help us treat a wide variety of conditions, from cancer to diabetes.

And the kicker is: bats probably have weird immune systems because they fly! Unlike gliding, flapping flight requires a huge amount of energy. So, bats have evolved ways to kick their cellular fuel production into high gear—mainly, by putting their mitochondria into overdrive.

Those are special compartments within cells that turn food into fuel. But there's a catch! When mitochondria convert nutrients into energy, they also create byproducts called reactive oxygen species.

So basically, mitochondrial exhaust fumes, in the form of really reactive molecules which contain oxygen. Now, these aren't all bad. The immune system uses them to rouse immune cells to action and kill bacterial invaders.

But, they can also cause a lot of damage. They can weaken cell membranes, mess with proteins, and even break DNA, and because of that, they play an important role in diseases like cancer and arthritis. Cells can try to keep them in check with antioxidants — compounds that essentially neutralize these overeager molecules.

But those can only do so much, and when the balance gets out of whack, cells experience a condition called oxidative stress. This is when most of the DNA damage happens. So, bats' supercharged mitochondria mean extremely high levels of oxidative stress—which, in turn, means constantly high levels of DNA damage.

But since bats don't immediately get super-cancer after their maiden flight, researchers have long suspected they've evolved ways to protect themselves from all this flight-related damage. And a few years ago, genetics studies found mutations which boost their ability to detect and repair damaged DNA. Essentially, they've also turbocharged the mechanisms that prevent genetically damaged cells from replicating.

Which may also explain why they don't seem to get cancers very often. So, bats produce tons of energy without damaging their cells. Sounds pretty awesome, really.

There's just one small problem. DNA damage can also be a sign of a viral infection, because viruses need to hijack the cell's genetic machinery to reproduce, and that process usually involves some strategic snipping. So, naturally, DNA damage triggers an immune response: inflammation.

Essentially, when cells detect DNA damage or other signs of infection, they chemically call in white blood cells. These cells kill and destroy pathogens using a variety of genetic and chemical tools. And they also help control how the inflammation unfolds—like, by bringing in additional white blood cells or switching some of them from germ-killing to tissue repair once the invasion is over.

This immediate or acute inflammatory response helps to get rid of the invaders and promotes healing. But remember, thanks to their supercharged mitochondria, bat cells experience constant DNA damage. They can repair this damage thanks to those advanced DNA-repair tools.

But the damaged DNA should still light an immune flare before it's fixed. So bats would experience super-inflammation all the time! And prolonged, chronic, and systemic inflammation isn't so great.

White blood cells and the processes they set in motion can be really destructive to the body's own tissues. In short, too much inflammation can lead to organ failure and even death. So flight should be a death sentence.

Except, bats have evolved some neat ways to knock down inflammation, too. For one thing, they dampen the activity of STING proteins. These proteins are one of the ways mammalian cells trigger an inflammatory response when a virus is detected.

Also, a genetic analysis of multiple bat genomes showed that they're the only mammals that completely lack genes for PYHIN proteins—another set of inflammation-triggering sensors activated by damaged DNA. And those are just part of the story. It will still be a while before we completely understand how bats prevent or dampen inflammation in their bodies, because it seems like every time they look, researchers keep finding more of these adaptations.

So to recap: we know that to make sustained flight possible, bats have ramped up fuel production and DNA damage detection while dialing inflammation down to a 1. But we know that inflammation is one of the big ways the immune system fends off intruders. So, doesn't that leave them open to all kinds of actual pathogens?!

And... The answer is yes! Around the turn of the 21st century, scientists discovered that bats act as a reservoir for a lot of viruses that are extremely dangerous to humans.

This includes filoviruses, which cause hemorrhagic fevers, like Marburg or Ebola. Also, henipaviruses like Hendra and Nipah, both of which can cause fatal brain infections … and, of course, coronaviruses, like SARS, MERS, and (most likely) the notorious new coronavirus that started the COVID-19 epidemic. And there's mounting evidence that bats were involved in transmitting these diseases to humans, either directly or indirectly, like by infecting farm animals.

Bats are also suspected of having given us other diseases in the past, like mumps, measles, and hepatitis B! But here comes another magic thing about bats:. Even though they're widely infected with notoriously deadly viruses, they don't actually seem to get sick from them.

The virus can be found in their bodies, but they don't have any symptoms. As for how that's possible? Well, we still have more questions than answers, but researchers have discovered a few evolutionary quirks about bat immune systems that help make that happen.

In part, that's because active viral infections in bats tend to be pretty short-lived, thanks to their hyper-vigilant interferon production systems. Remember how we said DNA damage is a signal of infection? That's because viruses try to reprogram cells to create copies of themselves.

But cells aren't sitting ducks during this process. In addition to calling out for help—which is that whole inflammation bit we discussed—cells have an internal defense mechanism. They can make a protein called interferon alpha, which activates genetic and chemical tools that reduce the virus' ability to multiply and spread.

Every other mammal we know of switches their interferon system on when an infection occurs. But genomic studies suggest bat cells always have their interferon alpha genes activated! This drastically cuts down the time it takes to react when a virus is present, so it allows bats to nip the infection in the bud before it becomes a full-blown disease.

And—of course—there's more. All mammalian cells contain an enzyme called ribonuclease L which, when activated, chops up viral RNA to stop a pathogen from spreading. But, in us and most other mammals, activating this enzyme takes a complex chain of steps—so it's not super quick.

But bats, on the other hand, can activate it directly with interferons, drastically speeding up infection containment. Scientists also think this fast activation of ribonuclease L helps bats outsmart viruses that have evolved to inhibit the enzyme before it can be switched on—something HIV does in humans, for example. So basically, when bats do get viruses, they're able to quickly clear them out… for the most part.

They can still fall prey to at least a few, like the rabies virus. And even quick suppression of a virus can mean it stays around in a group of bats. Bats tend to huddle close together when they roost.

Plus, they fly around in the same areas as bats from other colonies, and they're constantly spraying snot and saliva everywhere when they echolocate. So there's a good chance that, during that window when a bat has a virus that is actively replicating, it will spread it to another bat. That means even if each bat only hosts a virus for a short time, it can linger in the population.

And even this probably isn't the full picture. Mathematical models indicate that, by themselves, bats' social habits don't completely explain why they host so many viruses. Instead, research suggests that the viruses themselves have figured out how to lie dormant and undiscovered—like in the bats' lungs, spleens, or intestines.

And then, when the bat gets stressed—like when it's roused from hibernation—that stress temporarily dampens its anti-virus systems, allowing any hidden viruses to emerge. This leads to another period of increased viral replication and shedding. So again, the bat can transfer the infection to other animals.

Then, its antiviral systems get back up to speed, and the viruses are eliminated or driven back into hiding. Still, even when a virus is replicating and being shed, bats generally don't seem sick—not like a person would with the same virus. And that's likely because their inflammation-dampeners are still running.

So, they're still suppressing a lot of the immune response that would make them noticeably sick. And that may also be why viruses that are deadly to us aren't lethal to them. It turns out that the most severe symptoms of illnesses like MERS and Ebola, the symptoms usually responsible for their lethality aren't caused by what the virus itself does to the body.

Instead, they're the result of the destructive, catastrophic inflammation the virus triggers. This includes an extreme systemic reaction called a cytokine storm, where an over-release of pro-inflammatory signaling proteins turns a person's own immune system into their worst enemy. And some researchers think that our aggravated inflammatory response may actually be because these viruses have evolved to dodge the super-refined immune systems of bats.

Basically, they evolved to survive in a host that constantly and aggressively attacks their ability to replicate. So when that assault is suddenly weaker in a new host, they go wild and produce a lot of little virus babies that send the host's immune system into panic mode. This kind of overreaction can also happen to bats.

It's just not usually in response to viruses. Instead, it seems like their unique immune system may leave them vulnerable to non-viral invaders. The most infamous example of this is White Nose Syndrome, a fungal pathogen which has devastated bat populations in North America.

Some researchers think the bats' dampening of inflammation —especially during hibernation—makes it easy for the fungus to infect the bat. Then, once the bat awakes, it's immune system does react—only, it goes too far, which can lead to the bat developing a life-threatening form of systemic inflammation. So, basically, the reason they die from white nose is similar to why we die from viruses like MERS and Ebola.

That may mean that the key to saving bats from this fungus (and us, from the deadly viruses they carry) may lie in further research on bats. And also, if we're being selfish, we have a lot of other diseases characterized by inflammation, like heart disease and diabetes. So studying their inflammation system may lead to treatments for our chronic conditions.

And the same goes for studies on the ways that bats keep viruses at bay. Right now, we only have effective antiviral drugs for about 10 of the more than 200 viruses that can infect humans, and very few broad-spectrum antivirals. If we can discover more of bats' tricks, we might be able to use them to develop therapies against the diseases they host and other dangerous viruses.

Plus, all this research might help us live longer. Many researchers think bats' immunological adaptations are also behind some of their other superpowers, like how they seem to rarely get cancer, or how they live incredibly long lives for animals of their size. Usually, little animals live fast and die young.

But Brandt's bats can live for over 40 years even though they only weigh 4 to 8 grams! So instead of looking at bats as species zero, we should think of them as flying keys to longevity and resilience. And in the end, they're going to be our allies in health, not our enemies.

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