Bacteria that trick and grow the immune system

THE IMMUNE The system has many weapons to counter hostile income earners. But what works for one may not be effective for another. Intruders can take advantage of this by misunderstanding the system as fighting an enemy. This takes time for the intruder to settle. It’s sneaky. However, Sneakier is an approach just discovered by Ruslan Medzhitov of Yale University.As he and his colleagues report ImmunityThey discovered a bacterium that induces the host’s immune system to release compounds.

The mammalian immune system has two modes of attack. Type 1 is used against bacteria and viruses. Type 2 against multicellular parasites such as worms. However, some invading bacteria provoke a Type 2 response when Type 1 is appropriate. Dr. Medzhitov decided to investigate in detail.

He and his colleagues Pseudomonas aeruginosaBacteria that cause stubborn infections in people with cystic fibrosis. They suspected that it was guiding the body to initiate an ineffective Type 2 reaction to it, and wanted to know how it was doing this.

To investigate the problem, they grew laboratory cultures of the types of epithelial cells that line the human respiratory tract and monitored gene expression profiles when exposed to the toxic enzyme LasB produced by bacteria. .. They found that LasB activates signaling pathways that move epithelial cells to make a protein called ampphiregulin. It forms the basis of thick mucus that is excellent for catching parasites. It also mobilizes immune cells called eosinophils, which are good at attacking multicellular parasites.

Type 2 error

The discovery alone is interesting because it helps explain why patients with cystic fibrosis with bacterial infections often develop large amounts of mucus in the lungs, even though there is nothing to counter the bacteria.But what was more intriguing was what happened when the researchers tried to grow. Pseudomonas aeruginosa For this mucus sample. As long as LasB was present, the bacteria did not just multiply, but actually consumed the mucus.but also Pseudomonas aeruginosa It tricks the immune system into causing inappropriate reactions and preying on the consequences. To make matters worse, Dr. Medzhitov also found that all this immune manipulation made the surrounding tissues more susceptible to allergies.

An allergic reaction is essentially an exaggerated and inappropriate type 2 immune response. Therefore, researchers wondered if the reaction caused by LasB could lead to persistent allergies.To find out, they sprayed infected mice Pseudomonas aeruginosa Egg white protein (often used as an experimental allergen) is used on days 1 and 7 of the 4-week experiment. In contrast, they did the same in some mice that were genetically engineered to lack the ability to produce amphiregulin when exposed to LasB.

They theorized that in the absence of worms, inflamed epithelial tissue in normal mice could instead identify egg white protein as an invader. This is exactly what happened. When injected with a small amount of egg white protein 2 and 3 weeks after the start of the experiment, normal mice showed a strong allergic reaction to it. In contrast, few mice did not contain amphiregulin.

These discoveries are attractive in their own right and pave the way for new approaches to the treatment of cystic fibrosis infections. In addition, if one bug evolves the way it milks the immune system in this way, it is likely that other bugs do so as well. With this warning, researchers are on the lookout for similar cases. ■■

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Bacteria that trick and grow the immune system

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