The ability to fight disease is a driving force in human survival. Inflammation has emerged as a key weapon in this process. As pathogens change and evolve, the immune system adapts to keep up.
However, to what extent might such evolutionary adaptations also give rise to autoimmune conditions such as lupus and Crohn's disease?
This was a central question in a recent Trends in Immunology review by two scientists from Radboud University, in Nijmegen, Netherlands.
To address the issue, first author Jorge Domnguez-Andrs, a postdoctoral researcher in molecular life science, and senior author Prof. Mihai G. Netea, chair of experimental internal medicine, examined studies in the fields of virology, genetics, microbiology, and immunology.
They focused on people of African or Eurasian descent and how their ancestral origins may have influenced their risk of autoimmune diseases.
Of particular interest was how common pathogens in different communities related to changes in people's DNA, particularly when this involved inflammation.
The team found that the genetic changes made it harder for pathogen infections to take hold.
Over time, however, it seems that inflammation-related diseases, such as inflammatory bowel disease, Crohn's disease, and lupus, have emerged alongside improvements in immune defenses.
The findings also suggest that the human immune system continues to evolve and adapt to changes in environment and lifestyle.
"There seems to be a balance," says Domnguez-Andrs.
"Humans evolve to build defenses against diseases," he continues, "but we are not able to stop disease from happening, so the benefit we obtain on one hand also makes us more sensitive to new diseases on the other hand."
He observes that autoimmune diseases in today's humans tend to emerge later in life. These would not have caused health problems for our ancestors because their lives were much shorter.
"Now that we live so much longer," he explains, "we can see the consequences of infections that happened to our ancestors."
One of the examples that Domnguez-Andrs and Netea cover in detail in their review is malaria.
"Among various infectious diseases," they write, "malaria has exerted the highest evolutionary pressure on the communities across the African continent."
Malaria is a mosquito-borne disease that makes people very ill with flu-like symptoms, such as chills and a high fever.
While there has been much progress in the fight to control and eliminate the potentially fatal disease, it continues to threaten nearly half of the world's population, according to the World Health Organization (WHO).
The cause of malaria is parasites belonging to the species Plasmodium. These parasites spread to humans through the bites of infected female Anopheles mosquitoes.
Domnguez-Andrs and Netea note that Plasmodium has been infecting people in Africa for millions of years. During that period, the immune systems of those human populations have evolved stronger resistance to infection by increasing inflammation.
However, the downside of increasing inflammation to withstand infectious disease is that it favors health problems that tend to occur later in life.
Modern humans of African descent are more prone to developing such conditions, which include atherosclerosis and other cardiovascular diseases.
Another example of how ancestral changes in DNA leave imprints in the immune systems of modern humans is the interbreeding of early Eurasians with Neanderthals.
Modern humans whose genomes harbor remnants of Neanderthal DNA have immune systems that are better able to withstand staph infections and HIV-1. However, they are also more prone to asthma, hay fever, and other allergies.
Improvements in technology are making it more possible to find the downsides that can accompany disease-fighting adaptations.
Next generation sequencing, for example, is allowing scientists to delve more deeply into what happens at the DNA level between pathogens and the organisms that they infect.
Not only is new technology getting better at revealing genetic changes that occurred in our ancestors, but it is also showing that the human immune system continues to evolve and adapt.
In Africa, there are still tribes that hunt for food as their ancestors did. Thanks to new tools, scientists can see how the gut bacteria of these tribes are more diverse than those of, for example, contemporary African American people, who buy food in stores.
Other changes that have had an effect on DNA are the improvements in hygiene that have occurred in recent centuries. These have reduced exposure to pathogens and the diversity of gut bacteria.
"This reduced microbiota diversity in Western societies," the authors observe, "has been associated with a higher incidence of the so-called 'diseases of civilization,' such as cardiovascular diseases, diabetes, obesity, and autoimmune disorders, which are very unusual in hunter-gatherer societies, compared with communities living a Western-type lifestyle."
Domnguez-Andrs and Netea are extending their research to populations whose ancestry is other than African or Eurasian.
"Today, we are suffering or benefiting from defenses built into our DNA by our ancestors' immune systems fighting off infections or growing accustomed to new lifestyles."
Jorge Domnguez-Andrs, Ph.D.
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