Good immune health may come at the expense of chronic inflammation

Having an immune system robust enough to live a longer life can occur at the cost of chronic inflammation. Certain immune cells are under an inflammatory form of death that has evolved to protect us from infections, but they also sometimes do it at random, when no pathogenic agent is present, which triggers continuous inflammation which has been linked to a range of health complications.

Our innate immune system includes a group of cells that quickly respond to invading pathogens, such as viruses and bacteria. These cells generally feel microbes when they take fragments or are infected.

“Based on a little information, such as a viral DNA molecule, the immune cell has only a few minutes to decide what to do, and the decision is often to commit suicide; In a way, this altruistic suicide that amplifies inflammatory signals, ”explains Randal Halfmann at the Center for Cancer of the University of Kansas.

We already knew that this form of cell death, called pyroptosis, is triggered by domain proteins. These generally float simply in innate immune cells, but when they come into contact with a pathogen, they assemble in crystal type structures. They then activate another protein that kills the cell by hitting the holes, which made it break and release inflammatory signals which help the immune system to clean the pathogen.

To better understand this process, Halfmann and his colleagues have carried out a series of laboratory experiences where they studied human death proteins in yeast cells. This allowed them to identify five types of these proteins with chemical properties which would make them more likely to spontaneously form crystal structures when a pathogen is not present. The researchers then used data collected previously to determine the levels of these proteins in non -infected human immune cells.

From this, they calculated that certain innate immune cells – such as macrophages, which engulf and destroy pathogens – contain the five domain proteins of death at sufficiently high levels to be able to assemble spontaneously to trigger cell death in the body. “If they are at sufficiently high concentrations, the particles are more likely to assemble chance in crystal structures at a given moment during the life of a cell,” explains Halfmann.

Such events can contribute to chronic inflammation, which is built with age and has been linked to various conditions, such as cancer and Alzheimer’s disease, explains Halfmann. “It seems that we have evolved in this way to survive infections, but this can happen at the cost of chronic inflammation,” he said.

This path protects us from infections that represent a threat from birth, which gives us more chance of living in old age, but this can also mean that we are faced with an inflammation disease later in life, explains Halfmann. “If these small fires take place throughout life, the inflammatory damage that has been made can accumulate over time,” explains Andy Clark at the University of Birmingham, in the United Kingdom.

The development of drugs that prevent cells from dying spontaneously could potentially reduce chronic age -related inflammation, says Halfmann. But Clark stresses that it would also make people more sensitive to infections, a compromise that may not always be worth it.