Method Developed to Decode Immune Cell Swarms in Sepsis

Despite the best efforts of ICU staff and the most advanced life support, sepsis remains a common cause of death that Bryan Yipp, a critical care physician and clinician-scientist at the University of Calgary Cumming School of Medicine, witnesses often.

"Sepsis is the body's overwhelming immune response to an infection and sometimes that response can cause death," Yipp says. "While many cases involve people with long term illnesses, seemingly healthy people can be at work or home one moment and then within hours be admitted to ICU." Yipp says a recent discovery from his lab, published in Science, could lead to new treatments for the condition. 

When someone becomes septic, their immune cells cluster together, clogging the circulatory system and reducing or stopping blood flow, which causes organs to begin failing. To study this clustering, researchers combined two established scientific techniques to analyze the cells' behavior.

"We saw immune cells carry out complex swarming behaviors like bird murmuration. Just like the aerial ballet performed by a flock of birds, the synchronization of the cells was powerful and mesmerizing. But then we wondered, how are we going to make any sense out of it?" says Yipp, principal investigator on the study. "We developed a new method of combining microscopy with digital informatics to create something we coined cellular behavioromics."

Rather than treating the cellular images as pictures, the team recorded each cell's features, including its shape, size, speed, and direction of movement. Those features were converted into numerical data and fed into a bioinformatics pipeline.

"Our approach enabled us to sort out the cells. We found 18 different clusters of behaviors involved in the cellular swarms during sepsis," says Luke Brown, first author on the study. "Understanding cell behaviour can provide insight on new treatments including when to administer the treatment."

Yipp says this new understanding led the team to examine treatment options at different intervention points that could prevent cells from clustering. "The findings allowed us to propose targeted therapeutics to block bad host responses and allow good host responses to improve survival during sepsis," he says. "Currently, the treatment gold standard for sepsis is to administer antibiotics within an hour of deciding that someone is septic. We wondered whether an additional medication used in conjunction with the antibiotics would be beneficial."

In mice, the researchers found that a well-known, safe asthma medication prevented certain cells from clustering. Yipp says there is still much investigating to do, but given that sepsis affects and often kills millions of people worldwide each year, the results underscore the real-life importance of using computational biology to discover new therapeutics.