Bacteria collected from more than a mile below the surface of the Pacific Ocean may have just blown one of immunology's longest-held assumptions clean out of the water.
This totally contradicts one of the classic tenets of immunology – that the human immune system evolved to be able to sense every single microbe so it could catch the infectious ones.
"The idea was that the immune system is a generalist, it doesn't care if something was a threat or not, it just got rid of it. But no one had really pressure tested that assumption until now," Jonathan Kagan, an immunologist at Boston Children's Hospital and one of the study leaders, told Live Science.
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To test this, the researchers had to find bacteria that were unlikely to have ever had previous contact with mammalian immune systems. They chose a spot deep in the central Pacific Ocean, in the Phoenix Islands Protected Area in Kiribati, 1,650 miles (2,655 kilometers) southwest of Hawaii.
"It's not just the deep ocean, but the most deep, ancient, remote, and protected part of the ocean," study co-author Randi Rotjan, a Boston University marine ecologist, told Live Science.
"It's 4,000 meters (13,100 feet) deep; there are no resident mammals; and it's on the equatorial space where there wouldn't even be any whales for there to be any whale falls," Rotjan said, referring to the fact that whales tend to breed in one hemisphere and feed in the other, and so they'd only cross the equator while migrating.
"This was a good place to plausibly find bacteria totally different from the bacteria we interact with on land."
Once there, researchers used a remote submarine to collect marine bacteria from samples of water, sponge, sea star, and sediment, before growing them into 117 culturable species.
After identifying the features of their bacteria, the researchers introduced 50 of the strains to mouse and human immune cells. To their surprise, they found that 80 percent of the microbes, mostly belonging to the genus Moritella, escaped detection. The receptors on the mammalian bone marrow immune cells used in the study were incapable of seeing them.
"It was really surprising," Kagan said. "What you end up with is a picture of the immune system as being locally defined by the bugs that it lives near, and that the bugs and the immunity co-evolved. If you take your immune system into a different ecosystem, a lot of the bugs there will be immuno-silent."
For instance, Kagan added, "it's possible that there's an invertebrate animal in the deep Pacific Ocean that's blind to E. coli."
To try to narrow down which features of the marine bacteria made them invisible to our immune receptors, the team also exposed the mouse and human cells to just one specific part of the bacterial cell wall, called the lipopolysaccharide (LPS). Mammalian immune systems are known to use this outermost part of the bacterial cell wall to recognize so-called gram-negative bacteria and put up a fight.
The researchers found that the mammal cells' receptors were blind to the LPS on its own, too.
"The LPS molecules looked similar to what you'd find in bacteria on land, but many of them were completely silent," Kagan said. "This is because the lipid chains on the LPS turned out to be much longer than the ones we're used to on land, but we still don't know why that means they can go undetected."
Despite their spooky ability to evade detection, the researchers said that deep-sea bacteria don't pose any risk of infecting people.
"Firstly, they haven't evolved to evade mammalian immune systems, so if there was any pathogenicity it would be accidental," said Rotjan.
"The second reason it's highly unlikely is that the temperatures, pressures, and the chemical environments inside our bodies are so different to what you'd find at the bottom of the ocean. These bacteria aren't happy for more than a few minutes outside of their normal habitat."
Now that the researchers have laid the groundwork for how these alien bacteria interact with our immune systems, they plan to apply this knowledge to help develop better immunotherapeutics. They also hope to return to Kiribati to examine the immune systems of the organisms that these bacteria have evolved to infect.
The researchers published their findings online on March 12 in the journal Science Immunology.