Deconvolution of Neutrophil Heterogeneity in Pediatric Sepsis
Sepsis is an important problem in pediatric medicine, causing as many deaths in children as does childhood cancer. Sepsis is initiated by infections with bacteria or viruses. Despite antibiotics and vaccines, in some patients, the body’s inflammatory and immune responses intended to control the infection, can become excessive and poorly controlled, and consequently cause damage to the person’s tissues and organs. Understanding these abnormal responses is an unmet need in the field that could lead to new therapies to improve the outcome of children with sepsis.
The current proposal is focused on neutrophils, which are major white blood cells of the immune system that allow us to fight infection. It has become apparent that not all neutrophils are the same. Rather, there are beneficial neutrophils that allow us to clear infections, but there are also detrimental neutrophils that cause excessive inflammation and can thus cause tissue injury during sepsis. The current proposal will measure gene expression in individual neutrophils from patients with sepsis using new technology. By measuring gene expression with this degree of precision, we expect to identify beneficial and detrimental groups of neutrophils. This will be a first step in designing therapies for sepsis that can eliminate the detrimental neutrophils, while at the same time allowing the beneficial neutrophils to combat infection.