Discover new weapons of the immune system

It has been the focus of pharmacologists and toxicologists because it recognizes toxins in the environment. However, it also plays an important role in the immune system. A scientific team led by Max Planck's Infectious Biology Research found that bacterial virulence factors that have invaded the human body also bind to aromatic hydrocarbon receptors. Therefore, the innate immune response is activated and these factors are immediately broken down. Based on this finding, the scientists identified a component of the immune system that has hitherto been unknown: bacterial virulence factors can not only be neutralized by antibodies, but can also be directly destroyed.

Until now, immunobiologists have largely ignored the possibility that the immune system can directly destroy bacterial virulence factors. The aromatic hydrocarbon receptors expressed in many cells, including immune cells and epithelial cells, have a more surprising effect. So far, the receptor is mainly called a binding site for environmental toxins. The most harmful of these environmental toxins is TCDD - even tiny concentrations can cause fatal organ damage. However, it occurs from a variety of organisms, from insects to insects to humans. If it exists in so many organisms, the reason is of course not only to identify toxic substances in the environment, but to fight infection.

Therefore, the researchers began to identify bacterial molecules that are structurally similar to the known binding partners of aromatic hydrocarbon receptors. They found that the bacterial pigments they were looking for should protect against pathogens rather than damage the body. Mathematical models show that two blue-green phenazines of Pseudomonas aeruginosa can cause respiratory infections in hospitals, yellow naphthoquinone tuberculosis of Mycobacterium tuberculosis pathogens, and binding pockets to the receptor. (binding pocket) matches.

Then, mouse experiments confirmed how important the aromatic hydrocarbon receptor is to the immune system. With the infection of lung pathogens, animals without these receptors can develop more severe symptoms, have more bacteria in their lungs, and are more likely to die. Obviously, without an aromatic hydrocarbon receptor, the immune system cannot identify the enemy as early as possible. For pathogens, bacterial virulence factors are blessings and curses: on the one hand, they promote host infections, but on the other hand, they help the host find microorganisms.

The aryl hydrocarbon receptor is unique in that it directly binds to bacterial pigments and then triggers several genes in the nucleus responsible for the breakdown of virulence factors. To this end, it moves from the outside to the inside of the nucleus where it binds to DNA. The aryl hydrocarbon receptor combines the effects of the receptor and the transcription factor to provide a rapid response to infection. Instead, other receptors of the immune system must rely on accessory proteins that convey information about the pathogen entering the nucleus.