Researchers have discovered a therapy that targets host cells rather than bacterial cells in treating bacterial pneumonia in rodents. The method involves white blood cells of the immune system called macrophages that eat bacteria, and a group of compounds that are naturally produced in mice and humans called epoxyeicosatrienoic acids or EETs.

According to the World Health Organization, pneumonia caused by Streptococcus pneumoniae, or pneumococcal pneumonia, is the leading cause of pneumonia deaths worldwide each year. While physicians usually prescribe antibiotics to treat this severe lung infection, treatment is not always successful, and in some cases, the bacteria become resistant.

Matthew Edin, Ph.D., a scientist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, wanted to find a way to augment the body’s immune system to resolve the infection.

To keep tissues healthy, EETs work to limit inflammation, but during infections caused by S. pneumoniae and other microorganisms, inflammation ramps up after lung cells induce certain substances that prompt macrophages to gobble up the bacteria. Edin and colleagues found that one way to get macrophages to eat more bacteria is to decrease the ability of EETs to do what they normally do, which is limit inflammation.

Edin led the team that found infection induces a protein called soluble epoxide hydrolase (sEH) that degrades EETs. In contrast, when sEH is blocked, EET levels skyrocket, hampering the macrophages’ ability to sense and eat bacteria. As a result, the bacteria continue to reproduce in the lung, which leads to severe lung infection and death.

At the other end of the spectrum, blocking EETs using a synthetic molecule called EEZE boosted the eating capacity of the macrophages, leading to reduced numbers of bacteria in the lungs of mice. The scientists saw the same result when they placed bacteria and macrophages harvested from lung and blood samples of human volunteers in test tubes at the NIEHS Clinical Research Unit.

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Materials provided by NIH/National Institute of Environmental Health Sciences. Note: Content may be edited for style and length.