The naked mole rat’s secret to better immunity

In naked mole rat societies, the royals don’t wield scepters or don crowns. But that doesn’t mean her majesty is subtle. The toothy, pruney rodents live in tight-knit underground communities of up to about 300 members apiece, ruled by a tyrant queen who refuses to be mistaken for another bald-headed rabble. She climbs the social ladder through a series of brutal struggles and takes her throne as the only fertile woman in the group; She spends the rest of her sometimes decades-long life reminding her ailing relatives who’s boss. “She’s always shoving and shoving the other animals around” and literally will go over any subordinates she meets, says Gary Lewin, a neuroscientist at the Max Delbrück Center for Molecular Medicine in Germany. It’s her way of keeping the colony’s lower mortals in check – lest a lower-ranking woman come up with bright ideas and attempt a bloody coup.

Such prestige is hard-won, but the perks seem worth the pain. Naked mole rat societies, from matriarchs to the lowest subordinates, are ordered along status spectrums. The higher rodents rise in the hierarchy, the greater their chances of being vigorous and of living to ultra-old ages. in giving birth to offspring and avoiding the grunt work of nest cleaning, food gathering, and territorial defense; and, it appears, in growing an unusually large spleen. Among the naked rat nobles, the blood-filtering organ that houses, nourishes, and manufactures a menagerie of immune cells tends to be quite plump and elongated, as if stretched out like toffee. The connection between the spleen and social status is as strange as it sounds. “This is not the case with any other animal known to us,” Lewin told me. And perhaps even stranger, congestion appears to be an advantage.

In the eyes of most doctors and veterinarians is an enlarged spleen not a good thing. The organ swells when a person or animal is injured or infected and is in dire need of immune boosts. “The statement ‘bigger spleen’ is another way of saying ‘okay, your body is fighting something,'” says Dana Lin, an evolutionary biologist at Duke University. This also applies to naked mole rats: the spleen expands when nasty microbes are on the move and then shrinks again.

But Lewin and his colleagues found that the spleens of higher-ranked mole rats may also be larger to start with and may play an outsized role in defense. Colonial elites may gain more than classic skills as they move up the chain of command. They could also gain oversized organs that are better able to keep pathogens at bay.

The findings are still at an early stage. “I wouldn’t bank it yet,” says Jenny Tung, an evolutionary biologist at Duke who oversees Lin’s work; none were involved in Lewin’s new study. But if the results hold, they will join a growing research group determining social status as powerful sculptors of immunity in all types of animals. A few years ago, Tung led a team of scientists to show that rhesus monkeys, which also live in hierarchical groups, have their own status-sensitive immune system; Lower ranked monkeys, the common target of bullying, are disproportionately affected by inflammation. Similar patterns appear to play out among people of low socioeconomic status, whose bodies appear to experience far more stress and end up being less protected against disease.

The naked mole rat narrative likely has its own quirks given how bizarre these rodents are. Naked mole rats can live to over 30 years — about 10 times the length of a typical laboratory mouse — and are rarely plagued by the cancers that plague humans as they age. They are insensitive to certain types of pain and can survive a whopping 18 minutes without oxygen; They eat plenty of their own feces. All of these features, Tung points out, somehow overlap with immunity and, by extension, with immune organs like the spleen.

Valérie Bégay, a cancer biologist who led the spleen work in Lewin’s lab, first noticed the possible link between rodent rank and spleen size a few years ago when she was dissecting the animals for another project. Some of the animals on her table, she noted, had much larger spleens than others, sometimes twice or three times the size of their more petite counterparts as measured by total body mass — a difference she didn’t see in other rodents like mice. And yet all the mole rats on Begay’s table were healthy, with no infection in sight. That “made no sense,” she told me.

So the search for an explanation began. The souped-up spleens weren’t the product of some stealth disease or wild genetic anomaly; they were, to all appearances, fairly normal organs, only oddly huge. Bégay also found no evidence that the animals’ livers — another organ recruited in battles against pathogens — shrank or swelled in the same way, suggesting the spleen was somehow unique. The clearest link she and her colleagues could pull out was between a naked mole rat’s spleen size and its own rank: The more respected the naked mole rat was in its community, the larger the organ tended to be. When the researchers divided the spleens into two groups, large and small, about 75 percent of the small ones belonged to the lowest social class of their respective colonies. Bégay and her colleagues also analyzed the contents of the trimmer spleens and found that not only were the organs smaller, but they also appeared less equipped to launch a strong immune response.

Researchers don’t know which comes first: the taut spleen, the social cachet, or a third X-factor that could trigger both. Unraveling these relationships “is the million-dollar question” and requires experiments that track spleen size over time, perhaps as young rodents compete for a spot at the top of the social pyramid, says Melissa Holmes, an expert on naked mole rats at the University of Toronto, who was not involved in the study. In one scenario, some mole rats might be born with a thicker spleen that helps their host achieve higher social ranks by providing additional immune defenses. In another, which Lewin prefers, the mole rats scurry up the colony ladder first, unlocking a Swollen Organs achievement at each step along the way. Exactly how that would happen is a mystery. Perhaps repeated brawls for supremacy—especially when they take on a tinge of ferocity—boost a mole rat’s immunity so often that the spleen begins to bloat. Or maybe it’s some crazy hormonal phenomenon. That wouldn’t be unusual for mole rats: after the queen takes her throne, all other females’ genitals shrink spectacularly, rendering them sterile. Even some spleens of simple workers could become nasty.

The differences in spleen size can have a particularly big impact on naked mole rats, whose immune systems are somehow weak and odd. In humans and other rodents, almost all immune cells are made in the busy center of the bone marrow. Mole Rat Marrow, on the other hand, looks strangely empty and dormant. And although the weave produces plenty of blunt, rapid action innate Immune cells that can fight off most alien bugs devotes far less resources to the more accurate one adaptive fighters such as B. Antibody-producing B cells that other mammals rely on to quell the worst threats of infection.

This makes the mole rats very susceptible to certain viral diseases. Outbreaks in their colonies that are not well kept at bay can lead to mass deaths. In labs, the few survivors who emerge from these contagious skirmishes tend to be — surprise! – of higher rank. A lot could explain this bias, considering colony kings have so many health benefits on their side. But it’s hard to imagine, Lewin said, that a bougie spleen isn’t at least partly to blame.

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