New route to the control of sepsis

Might a short piece of DNA hold the key to controlling sepsis?

When bacteria infect us, the fantastic machinery of the human immune system kicks in. Specialised immune cells, armed with a slew of chemicals, go into battle to combat the invader. Some engulf the organisms and regurgitate parts of them onto their surfaces to stimulate other the elements of the immune system. This can include the production of antibodies, which are sticky molecules that bob about in the blood and are also present in the body's secretions where they can stick to and neutralise threats they encounter.

Usually, the immune response is highly controlled, but sometimes it can go bad! Organisms can get into places where they shouldn’t be, like the blood, and start to grow. This can activate the immune system throughout the body. Immune cells switch on to carry out the ‘final biological reaction’. This is a last ditch attempt to remove invaders, but the system overreacts and can kill us in the process. This is what occurs during sepsis.  

Now, in a paper published this week, researchers from the University of California, Santa Cruz and the University of Texas have shown that a small piece of genetic material regulates growth of immune cells and could have a role helping to protect animals from the devastating consequences of sepsis.

Co-author of the research paper Susan Carpenter said, "We're really trying to get at the heart of sepsis and what genes are involved in regulating the process."

The pattern for the building blocks of our body, our proteins, is stored in our DNA. This uses a process called transcription to convert it to RNA. Another mechanism called translation makes proteins from the RNA molecule. We could think that this happens most of the time but interestingly, most RNA does not actually go on to make proteins. These so called "non-coding" RNA’s have other roles governing biological processes. The research team have identified a non-coding RNA called GAPLINK. They found when they removed the genes that produce it in immune cells of mice; they could survive a simulated infection that would normally result in sepsis and death.  

"There's so many genes involved in these responses that just removing this one in particular can have the strong impact. It's not unusual, we see this with particular proteins. If you remove them from the system, they can have positive impacts," explains Carpenter.

The work published in the Proceedings of the National Academy of Sciences journal shows how previously unknown molecules that have a role in the immune response could one day pave the way to a better understanding and treatments for sepsis in humans.