Medical

Synthetic molecule boosts bacteria-eating immune cells to treat pneumonia

Synthetic molecule boosts bact...
An illustration of macrophages destroying bacteria
An illustration of macrophages destroying bacteria
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An illustration of macrophages destroying bacteria
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An illustration of macrophages destroying bacteria
A microscope image of S. pneumoniae bacteria (green) being consumed by a macrophage in a mouse
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A microscope image of S. pneumoniae bacteria (green) being consumed by a macrophage in a mouse

Pneumonia is usually treated with antibiotics, but unfortunately these drugs are becoming less useful as bacteria develop resistance to them. Now, researchers at the National Institutes of Health (NIH) have found a way to boost immune cells to eat the bacteria more effectively, potentially leading to a new pneumonia treatment.

Decades of overuse of antibiotics has led many species of bacteria to develop resistance to the drugs. Alarmingly, our last line of defense is beginning to fail and we might be on the cusp of a health crisis that could claim up to 10 million lives per year by 2050. New antibiotics can help slow it down, but alternatives are desperately needed.

One such alternative is to target the host’s immune system instead, and give it a helping hand in the fight against the invaders. For the new study, the researchers looked to the complex interplay between immune cells called macrophages, inflammation and bacteria.

Macrophages patrol the body for things that shouldn’t be there, engulfing and destroying dangers like bacteria. They’re summoned to sites of inflammation by other immune cells, and can increase it if they need more assistance. But of course, inflammation can be a bad thing too, damaging tissue and causing pain if it goes on too long.

Compounds called epoxyeicosatrienoic acids (EETs) perform a regulatory function by limiting inflammation. However EETs are suppressed during infections to allow inflammation and immune cells to kill the invaders. So for the new study the researchers blocked EETs even further, using a synthetic molecule called EEZE.

The team tested the molecule in mice infected with Streptococcus pneumoniae, a bacteria that commonly causes pneumonia. And sure enough, the mice that received doses of EEZE had far reduced numbers of bacteria in the lungs than control mice.

A microscope image of S. pneumoniae bacteria (green) being consumed by a macrophage in a mouse
A microscope image of S. pneumoniae bacteria (green) being consumed by a macrophage in a mouse

Follow-up tests were conducted in human cells in the lab. The researchers harvested macrophages from lung and blood samples, and placed them in test tubes with bacteria. Those that were also given EEZE killed more of the bacteria than those without.

Of course there’s no guarantee that results of animal tests will translate into humans, but the team says it opens up a new avenue of research.

“EEZE is safe and effective in mice, but scientists could develop similar compounds to give to humans,” says Matthew Edin, co-lead author of the study. “These new molecules could be used in an inhaler or pill to promote bacterial killing and make the antibiotics more effective.”

There’s another potential issue though. EETs play an important role in regulating inflammation, and in some contexts they’re needed – for instance, the compounds suppress cardiovascular inflammation, which can improve cell survival after stroke or heart attack. Care needs to be taken when administering EEZE or developing similar drugs that work on the same mechanism, to ensure that it doesn’t interfere with the beneficial role.

The inverse may also need to be accounted for. Other studies are testing anti-inflammatory drugs that work by increasing EET levels, and the researchers on the new study caution that increased chances of bacterial infections like pneumonia could be a potential side effect.

The new study was published in the Journal of Clinical Investigation.

Source: National Institute of Environmental Health Sciences

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