It’s tough at the bottom of the totem pole. A low status isn’t just bad for your social life, it’s also bad for your immune system, raising your risk of infection and disease. But according to a new study in monkeys, this effect is reversible: Climbing the totem pole can cause the immune system to rebound.
Researchers have long known that low social status is associated with poor health and shorter life span. But until now, studies were mostly correlational; it wasn’t clear whether low social status led to poor health, or whether poor health led to low social status. For example, low status individuals—like the homeless—tend to be exposed to more microbes and toxins, lack access to high-quality food and shelter, and often engage in risky behaviors like smoking, drinking, and drug use. All of these things can cause poor health. But is poor health itself enough to trigger the plunge into homelessness?
“Often, when we isolate those physical risks, you can still see some indication that mere inequality … has some kind of biological consequence,” says Steve Cole, a neuroimmunologist at the University of California, Los Angeles, who was not involved in the study. “And that idea is a little more controversial.”
To address this issue, researchers turned to rhesus macaques, which have hierarchical societies. Monkeys at the top of the pecking order are more likely to groom each other, which helps form social bonds, whereas monkeys at the bottom are more likely to be attacked instead. To manipulate the pecking order, the team introduced captive female macaques into new social groups where they didn’t know anyone. The order in which the monkeys were introduced strongly predicted their dominance rank: The one introduced first tends to become the alpha, the one introduced second tends to become the beta, and so on.
After 3 months, the researchers drew blood samples from the monkeys, purified five different types of immune cells, and measured gene expression across their entire genomes. They found that the activity of more than 1600 genes was significantly affected by social status in natural killer cells, a type of white blood cell that kills virally infected cells and tumor cells in the body.
To see whether these changes actually mattered, the researchers collected more immune cells and challenged them with a simulated bacterial infection. Immune cells from low-ranking monkeys were less effective at fighting the infection, the team reports today in Science.
The scientists then asked whether this effect was reversible. They created new groups of monkeys unknown to each other, and changed their ranks by changing the order in which they were introduced into the new groups. The researchers found that the gene expression levels in immune cells changed in response to the macaque’s new social rank within 3 months of establishing the new groups, and the cells got better at fighting infection.
“I like to think there is a positive societal message,” says author Noah Snyder-Mackler, an evolutionary anthropologist at Duke University in Durham, North Carolina. “If you take an individual out of their poor social environment, at least in these adults, you’re able to reverse the effects on their immune cell function.”
But the findings also raise questions about how best to help low-status individuals. “It may not be sufficient just to equalize access to healthcare, or protection from microbes and toxins,” Cole says. “What else do we need to do?”
One caveat of the study is that the researchers did not control for the early life history of the adult macaques, even though many studies have shown that early life adversity can have lifelong effects on health, says Michael Kobor, an epigeneticist at the University of British Columbia in Vancouver, Canada, who was not involved with the work. Another thing the team didn’t consider was genetic differences among individuals: Some monkeys are naturally more susceptible to adversity whereas others are more resilient, he says.
Nevertheless, Kobor says, “This is super well done. It’s going to set the bar for subsequent studies very high.”