Rare White Blood Cells Could Play Critical Role in Sepsis Prevention

Sepsis is a deadly health threat that affects more than 75,000 children in the United States each year. Approximately 7000 of these pediatric patients die from infection and many of the children who do survive are left with debilitating health challenges. The rates of morbidity and mortality are estimated to be even higher in developing countries. Yet despite the deadly implications of this infection, very little is known about what exactly breaks down in the immune system of a child is fighting off an infection that leads to sepsis.

Now, a team of international investigators have discovered that a rare group of white blood cells called basophils play a critical role in inducing immune responses against infections and preventing the development of sepsis. Investigators from Seattle Children’s Research Institute, along with Stanford University School of Medicine and other international labs, are hopeful that the discovery can inspire future research on ways to prevent sepsis.

"Sepsis is the number one killer of children globally, yet little is known about what goes wrong in an individual's immune system to cause sepsis as it fights off an infection," Adrian Piliponsky, PhD, a principal investigator in the research institute's Center for Immunity and Immunotherapies, said in a statement. "Without this information, it's hard to predict who will develop sepsis or explain why sepsis causes a range of immune responses in different individuals."

For the study, the investigators traced immune responses back to the early stages of infections and focused on the basophils, which are thought to play a role in enhancing immune defenses against bacterial infections. According to the investigators, basophils make up less than 1% of a person’s white blood cells.

In a paper published in Nature Immunology, the investigators detail using a model of bacterial infection and sepsis that closely resembled the progression and characteristics of human sepsis in genetically-modified mice.

Their studies demonstrate that basophils were one of the first immune cells to appear at the infection site. Once the basophils arrived, the investigators observed that the cell released a protein known as tumor necrosis factor, which resulted in enhanced inflammation in immune response to the infection and improved survival in the mice.

The paper also explains that in mice deficient in basophils were found to exhibit reduced bacterial clearance and increased morbidity and mortality related to sepsis.

The protein signals other cells to generate inflammatory responses that heal and protect damaged tissue. The investigators believe that this finding backs up evidence that basophils can play a critical role in both the immune system’s defense against an infection and that a deficiency or reduction of basophils can result in sepsis.

“Together, these findings provide novel insights into how basophils, and basophil-derived [tumor necrosis factor], might have key roles in the early stages following bacterial infections and in resisting the progression of such infections to sepsis," the investigators write in the paper.

The investigators are hopeful that the findings will lay the groundwork for future projects. By investigating certain aspects of basophil function, it is hypothesized that the scientific community can determine better ways to assess an individual’s risk for sepsis or prevent the dysregulated immune response that can lead to sepsis.