Individuals surviving an episode of severe sepsis remain at increased risk for premature death from infection. The cause of this sustained immunosuppressed state has not been adequately explained. Our preliminary data suggest a sustained impairment in monocyte function that is a product of cell-intrinsic changes and, more importantly, altered cellular interactions. In this project, we will explore aspects of the phenotype and function of the post-sepsis splenic monocyte macrophage populations, the spleen cells that help contribute to the sustained reduced response to endotoxin challenge in vivo, as well as the potential contributory role of brain inflammation and the neural connection to the spleen. Overall, this project will identify cellular interactions that control monocyte phenotype function and regulation in vivo in the context of sepsis and will identify new pathways that can be therapeutically targeted even after the acute event to improve long-term outcome in this high-risk group.
Individuals surviving severe sepsis remain at risk for lethal infection. This project will study the splenic monocyte and how its function is altered by the experience of sepsis and how those alterations contribute to immune dysfunction. These studies have the potential to reveal new therapeutic targets to improve long-term outcome in sepsis survivors.
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