Mast cells in a frenzy
Macrophages belong to the white blood cells and are an important part of the immune system. As so-called phagocytes, they absorb other cells, pathogens or cell remnants and break them down. German researchers have now shown that these cells have two completely different faces. While they normally take on important tasks in healthy tissues, they switch to a normal attack mode when they are infected and go on a hunt.
In a current study, researchers from the Rheinische Friedrich-Wilhelms-Universität Bonn deciphered how macrophages blatantly change their metabolism in order to hunt and destroy pathogens. The findings could lead to new treatments for autoimmune diseases, among other things. The study was recently published in the specialist journal “Immunity”.
A nose for pathogens
As the research team reports, macrophages have numerous sensors on their surface with which they can detect intruders. One could even speak of "sniffing out" because the so-called toll-like receptors work similarly to the olfactory receptors in the nose.
Signal initiates attack mode
When the receptors perceive certain chemical signals, they are activated and trigger a kind of alarm. This alarm causes a number of reactions to be triggered inside the cell. "In this phase, macrophages initiate their inflammatory response," explains Mario Lauterbach from the research team. For the first time, the researchers deciphered how the macrophages change their metabolism and what effects this has.
A separate receptor for each "smell"
According to the current study, there are many different groups of toll-like receptors. Each group specializes in a different “smell”. In the course of evolution, this compilation has emerged in order to be able to react to the most important danger signals.
One of these receptors, for example, responds to lipopolysaccharides (LPS), which are important components in the cell walls of bacteria. "We have now confronted macrophages with LPS and examined what happens in the minutes and hours afterwards," said Lauterbach.
When macrophages attack
The scientists showed that the cell metabolism changes massively shortly after contact with LPS. First, the phagocytes absorb more glucose from their surroundings. Amazingly, the macrophages do not use the sugar to generate energy, but produce acetic acid-like acetyl groups from it.
DNA interference makes macrophages stronger
The acetyl groups created in this way are now attached like markings at certain points in the DNA in the cell nucleus. This loosens up the wound up DNA and certain genes can be read more easily and quickly. "These are, for example, hereditary systems that are responsible for the release of inflammatory messengers or improve the mobility of the macrophages," explains Lauterbach.
Fine tuning of the genes
According to the researchers, the discovered mechanism enables macrophages to fine-tune the genetic response to pathogens. This increases their effectiveness if they already know the pathogen, i.e. if the body has already been infected with them. This is a similar principle that vaccination takes advantage of and could lead to new vaccination strategies.
New starting points for therapies
The findings could also contribute to the development of new therapies for autoimmune diseases, since the immune response is misguided or too strong in many diseases such as rheumatism, diabetes or multiple sclerosis. "It is possible that the mechanism we discovered can be influenced in such a way that it inhibits harmful inflammatory mechanisms without too much suppressing the immune system as such," adds research director Professor Dr. Eicke bib. This can prevent the phagocytes from being permanently in attack mode without actual invaders. (vb)
Author and source information
This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
Graduate editor (FH) Volker Blasek
- Mario A. Lauterbach, Jasmin E. Hanke, Eicke Latz, u.a .: Toll-like receptor signaling rewires macrophage metabolism and promotes histone acetylation via ATP-citrate lyase; Immunity, 2019, cell.com
- Rheinische Friedrich-Wilhelms-Universität Bonn: How immune cells switch to attack mode (accessed: December 18, 2019), uni-bonn.de