Scientists investigating the immune system of modern humans have found significantly different responses in Europeans and Africans, and ancient breeding with Neanderthals tens of thousands of years ago could be partly to blame.
The discovery could explain why Africans are generally born with stronger immune systems than Europeans, and why they're more predisposed to certain autoimmune conditions.
"I was expecting to see ancestry-associated differences in immune response but not such a clear trend towards an overall stronger response to infection among individuals of African descent," says geneticist Luis Barreiro from the University of Montreal in Canada.
Barreiro and his team studied blood samples taken from 175 Americans – roughly half of which had African ancestry, with the other half being of European descent.
From these samples, the team extracted macrophages – immune cells that work to kill pathogens – and infected them with two kinds of bacteria: Listeria and Salmonella.
When comparing the samples 24 hours later, the researchers found that the macrophages from the African group had reduced the bacterial growth three times faster than the European group, thanks to a stronger inflammatory response.
In terms of combating these specific bacteria, that's a definite advantage, but the researchers point out that it also comes with certain disadvantages.
"The immune system of African Americans responds differently, but we cannot conclude that it is better," says Barreiro, "since a stronger immune response also has negative effects, including greater susceptibility to autoimmune inflammatory diseases such as Crohn's disease."
In addition to measuring how effectively the macrophages combated the pathogens, the researchers analysed the gene activity of these immune cells, and found evidence linking the European samples – but not the African blood – with Neanderthal DNA.
The team's hypothesis is that when early humans migrated out of Africa and into Europe around 100,000 years ago, they would have encountered a continent colonised by Neanderthals.
For thousands of years, it's possible that these two species did more than just co-exist alongside one another. The researchers suggest they also bred, which would account for why traces of Neanderthal DNA can be found in European blood.
If that's the case, it may have conferred an advantage in the new environmental conditions these early Europeans found themselves in – plus given them a general lowering of inflammation responses, which might have made sense outside of Africa's heat.
"Our results suggest that the immune systems of African- and European-descended individuals have evolved to better respond to the specific needs imposed by their specific environments," Barreiro told Live Science. "What is advantageous in one context is likely to be detrimental in another."
In a separate study, scientists in France compared the immune responses of 200 individuals, again divided by ancestry: 100 being of African descent, and 100 of European lineage.
This time, the team – led by researcher Lluis Quintana-Murci from the Institut Pasteur – looked at how immune cells called monocytes responded to bacterial and viral molecules, including the influenza virus.
The tests showed that, much like in Barreiro's findings, European immune responses to the pathogens were characterised by less inflammation than African responses. And just like the Canadian study, they also showed that Neanderthal-like genes in the European blood played an important role in how this worked out.
The team suggests that early Europeans "borrowed" genetic mutations from Neanderthals, including variants that regulate how the immune system responds to threats such as bacteria and viruses.
It's possible that in the colder climate of Europe, there was less need for inflammatory responses to head off dangerous pathogens than in Africa – and that adaptation could have provided another inherent evolutionary benefit too.
"Reducing immune inflammatory responses is a way to avoid autoimmunity, inflammatory, and allergic reactions," Quintana-Murci told ResearchGate.
"Finding that reduced immune responses has conferred an advantage highlights the tradeoff between recognising pathogens while avoiding exacerbated, aberrant reactions that can be also harmful for the host."
Both teams acknowledge that there's a lot more work to be done to better explain why our immune systems function so differently – but doing so could one day help us develop things like personalised treatments, or medications tailored for certain ethnicities.
And in addition to looking into the past, we also need to consider other societal factors that go beyond humanity's ancient ancestors.
"There is still much to do," says Barreiro. "[G]enetics explains only about 30 percent of the observed differences in immune responses. Our future studies should focus on other factors, emphasising the influence of the environment and our behaviour."