Human Immunity Evolution

I wanna have immunity, like no one ever was. To live well is my body's test. To train it is time's cause.....
14 December 2021

Interview with 

Mihai Netea, Radboud University Nijmegen

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When we come into contact with an infectious disease, our immune system is usually able to detect and destroy it. Indeed our bodies can tackle a wide variety of microbes. But it wasn’t always this way - we think our immune systems went up a gear about 8000 years ago. But how do we know this, and what gave human immunity this shot in the arm? Julia Ravey heard from Mihai Netea, from Radboud University, Nijmegen, who’s been using ancient DNA to find out...

Mihai - Our immune system is made to defend us against pathogens, and evolves depending on the interaction with these microorganisms. What is very important to realise, is the fact that along history, we changed a lot the infections with which we interact during our everyday life. 8,000 years ago we developed domestications of animals. And because we started to live very close to animals, the infectious burden very strongly increased, and the types of infections also changed, because now we took many more infections from the domesticated animals.

Julia - We have really great tools now for studying people's immune systems, but it's a bit harder to study people who lived 8,000 years ago. How did you investigate how our immune response evolved?

Mihai - Well, indeed, it's very difficult to study the immune system because we do not know those people who lived so many years ago, and we don't have their cells to study, and so on. However, one thing that we can study is how the genetic code, how our DNA changed during this period. Because now we know exactly what are the regions of the genomes, which are important for host defence. And we can see there, how those regions, important for host defence, have changed during the last couple of thousand years. And depending on how these changes took place, we can make predictions, whether our immune system works stronger or less strong or more tolerant against certain pathogens.

Julia - How did you find DNA from people who lived so long ago?

Mihai - Of course this is also not easy. And fortunately in Europe, we are lucky because of the type of climate that is here, which is not very, very hot. And especially for the bones that have been found, for example, in caves, which are in a natural refrigerator, let's put it this way. So we can isolate from small quantities of bone, especially from teeth, DNA, purify it and sequence it, and read precisely how does it differ from the DNA of the modern people?

Julia - The one perk of having bad weather is good preservation of DNA.

Mihai - Exactly.

Julia - By using our DNA as a sort of time machine, what did your research find?

Mihai - So what we have identified is the fact that our DNA and immune response changed significantly during the neolithic time period. So after the neolithic time period, when we came into contact with many more infections than previously, and that changes the way in which the immune system reacts. And in parallel with these changes that took place to help us in the fight against infections, it became clear that also the susceptibility that we have to certain immune mediated diseases that we have in modern times has changed as well. Just to give you an example, certain autoimmune diseases, such as multiple sclerosis or rheumatoid arthritis, which are very prevalent in the circulation. We would think that we are much more susceptible to those now, than thousands of years ago. Well, we discovered that that is not the case. In fact, the susceptibility to rheumatoid arthritis and multiple sclerosis decreased. That is not to say that nowadays less people have these diseases that they had previously, because of course thousands of years ago, people did not reach an age that they could develop these diseases. But in any case, our susceptibility to these diseases decreased. On the other hand, and this has to do probably with the type of diets that we had after domestication of animals and agriculture, we see an increase in susceptibility to inflammatory diseases of the gut. And this is very clear information that we obtain from these genetic studies.

Julia - It's really interesting how these results, from looking at our immune system responses thousands of years ago, can tell us information about potentially how we respond to disease causing bugs today. Do you think this work can be used in that way?

Mihai - Well, I do think that it makes us understand, what are the factors that are important for the susceptibility to infections, to inflammatory diseases, to other types of immune mediated diseases. And from drawing these conclusions, we can learn much better also nowadays, in what directions should we look for new types of therapies for the modern diseases. In the next period, we will investigate of course, how these differences in immune system change also between different populations around the world. This is something which is very important, because it tells us a lot about public health measures. How can we help people from various parts of the world? Where is the susceptibility higher or lower? How to predict what will happen in the future, because of the historical trends that are ongoing in the modern world. And hopefully this would help measures at the public health level to improve health in the populations. It's fascinating to have a mirror in the past, but at the same time, we try to help future generations with that, of course.

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