New defenses

DW-WORLD.DE: Professor Hoch, you have discovered a new immune mechanism that works in addition to our normal immune system. This new mechanism is linked to the metabolic status. Why do we have an extra immune system?

Michael Hoch: The defense system which we now found works in barrier epithelia like the intestine or the skin. If the body loses energy because it takes in fewer calories over a longer period of time, or because of stress or exhaustion, this additional defense system gets activated. The normal immune system cannot be active all the time, since there are bacteria on and in the human body that are helpful to us. They should not be fought. An infection only happens if the pathogenic, harmful bacteria cells have crossed the epithelia. The immune system works during an infection, the antimicrobial peptides are working when we don't have an infection yet.

What are antimicrobial peptides?

They are defense proteins that are used by the defense system to destroy bacteria before an infection happens. One assumes that they enter the membrane of the bacterial cell and destroy the cells by producing holes within. The antimicrobial peptides are little tornados, so to speak, which are sent out by body cells to destroy adversarial bacteria.

How do the antimicrobial peptides know which cells to destroy? How do they distinguish between helpful and adversarial bacteria?

That we don't know for sure. We know that if the energy level decreases, the system gets activated and several peptides are produced. But how they work, if one stimulates the good bacteria and how the pathogenic bacteria gets destroyed, that's not figured out yet.

So you are saying that the less food I have eaten, the more on-guard is my defense system?

Yes, you are more fit. Pathogenic bacteria that can be on or in your body at any time have less of a chance to overpower body cells and cross the barrier.

Doesn't it sound contradictory that our immune defense is said to be stronger if we have eaten less or if we are exhausted?

We have discovered a very old, evolutionary mechanism. It's a mechanism that presumably has worked in very simple organisms. These antimicrobial peptides, these defense proteins, they can be produced by bacteria as well. And they are produced by bacteria exactly when those bacteria have a rich nutrition source, they proliferate, and all of a sudden the nutrition source is ending. Then these bacteria begin to synthesize such peptides, to eliminate their competitors. This means we are talking about an evolutionarily old way to stop other bacteria from growing, by destroying them.

What happens if people eat too much?

When we take in too much nutrition, the peptides are reduced. Then this mechanism is not functioning, it's only working if I eat less over a longer period or if I am stressed. This means vice versa, if we eat too much, if we are overweight, then the defense functions at the barrier are declining. The result would be that people who suffer from diabetes or metabolic diseases are more likely to get infections in barrier tissues such as intestinal or skin tissues, because the barriers are getting fragile and the bacteria are able to intrude more easily.

Overweight people are more in danger?

Exactly. The fact that the cells have a surplus of nutrition and the metabolism in the cells is stimulated, leads to the production of fewer defense proteins.

And these peptides are also produced under stress?

You might have discovered the phenomenon where you have to finish something by a certain deadline, and up to this deadline you are busy and it costs a lot of energy. And people take some days off after all this stress, they often get sick. It's not known why this happens. I don't want to say that our mechanism is the only mechanism that causes this phenomenon, but it's a very interesting correlation. If you are under stress, the defense proteins at the barrier regions are activated, the pathogenic bacteria are being fought. And when we relax after all this stress, and we also eat very well during our vacation, then this immune system at the barrier has been reduced. And the likelihood of pathogenic bacteria destroying these epithelia and causing an infection is higher.

Does a stronger defense system with peptides also mean that we live longer?

Many different projects see a connection between lower-calorie nutrition, and increased age. People who take in fewer calories over a longer period of time – well-balanced, but fewer calories – can extend their life span. Our mechanism at the barrier regions would then be activated and efficiently fight those pathogenic bacteria over a longer period. We are examining right now if we live longer because the defense system at the barrier is activated. We are not able to say if it's the only cause for a longer life.

But compared to our ancestors we actually have more food available. Still we live longer. How does that go together?

Certainly, longer lives in industrial nations are linked to advanced medicine and our well-balanced diet. But we found that different animals – and this is probably true for men as well – that they can live longer, up to 30 to 40 percent if they ate fewer calories. This is very impressive, but it's still not clear why this is happening. And I think that this mechanism that we discovered is one aspect of it. Now we are trying to figure out how important this mechanism is in the whole process. The older we get, the more porous the barrier epithelia get and infections happen more frequently. This means the barrier plays a great role in the aging process. If we can strengthen the barrier, we could get older as well.

But less food does not mean to be hungry all the time?

No, I would not go that far. We also know what happens if someone does not eat enough. Nutrition needs to be well-balanced and sufficient, so that all body functions work properly. But you see, we are used to eating all the time and this does not go well with our species. If you go back in evolution, sometimes we ate a lot, but then we didn't eat much for weeks. When our ancestors were successful in hunting, they ate meat, but then again they had to eat roots and the like. In a sense our body functions are adjusted to that kind of behavior.

Michael Hoch is the Director of Molecular Development Biology of the research institute LIMES (Life & Sciences Institute) in Bonn.

Author: Sarah Steffen
Editor: Jennifer Abramsohn