About This Project

Sepsis is a life-threatening condition in which the body's immune response to infection injures its own tissues and organs. It is the number one cause of death in the critical care unit. To provide more effective treatment, it is crucial that we understand which cells and signals play a role in the immune response to infectious stimuli in sepsis. Our research is furthering this understanding and utilizing these findings to identify new treatments.

Ask the Scientists

What is the context of this research?

Sepsis is one of the most dangerous and complex diagnoses seen in critically ill patients. It is a clinical diagnosis broadly characterized by an abnormal physiologic response to an infection. The prevailing belief for many years was that a hyperactive immune system was responsible for the abnormal physiologic response as well as the morbidity and mortality associated with sepsis; however, there is growing evidence that a hypoactive or paralyzed immune response causes harm to patients. Our project aims to understand further the mechanisms behind the hypoactive immune response in patients with sepsis, with the goal of identifying potential therapeutic targets to help physicians diagnose and treat this diagnosis.

What is the significance of this project?

It is estimated that 3,000 new cases of sepsis are diagnosed and treated every day in US hospitals. Conservative estimates of the worldwide incidence of sepsis are 20 million per year with a mortality rate higher than breast, lung, and prostate cancer combined. Costs associated with treating a septic patient are approximately $32,000 per patient. Furthermore, research indicates that the incidence of sepsis is increasing. Thus, new directions in sepsis treatment are needed. Novel approaches to managing sepsis focus on stimulating the immune system. Our work will identify the cells and signals that orchestrate the hypoactive immune response, and will provide fresh insight on how best to treat sepsis.

What are the goals of the project?

Our experiments will look to understand how immune cells respond to bacterial stimuli. In particular, we will focus our research on the tissue resident macrophages, which have been shown in prior research to be implicated in the immune tolerance or immune paralysis seen in septic patients. Macrophages function as the linchpin of the host immune system, coordinating the efforts of the innate and adaptive immune systems. Our work interrogates why tissue resident macrophages rather than circulating macrophages seem to be primary drivers of sepsis-induced immune-paralysis. Our in vitro and ex vivo experiments have been previously described. In vivo work will involve patients with clinically diagnosed sepsis. The experiments will begin in late July 2017.