Resilience mechanisms in different species that may be translatable to humans
Abstract
The objective of the proposed research is to lay the scientific foundation for developing new host-based therapeutics . The inflammatory response of different species varies tremendously in sensitivity to the same microbial challenge. Humans are extremely sensitive to most inflammatory challenges . However, some species, including rodents, develop very little inflammation in response to very strong inflammatory stimuli. The investigators will study the relationship of bacterial killing in blood of mice and humans to activation of immune cells in blood, compare the inflammatory responses of mouse and human cells that line blood vessels, evaluate if anti-inflammatory responses mediated by mouse plasma are tuned by nerve activation, and compare immune cell responses of genes in blood of humans with that of baboons. Killing of several different species of bacteria will be compared in mouse and human whole blood and plasma with phagocytosis and induced cytokines in the same blood sample. The effect of mouse and human serum on the activation of endothelial cells will be compared . The overall long term aim of this proposal is to develop therapies for humans based on understanding the underlying mechanisms of resistance in species that tolerate a large inflammatory challenge, and then leverage this knowledge to develop therapies for humans with inflammation induced by infection.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 12, 2017
- Source ID
- W911NF1510601
Entities
People
- H. Shaw Warren
Organizations
- Army Contracting Command
- Defense Advanced Research Projects Agency
- Massachusetts General Hospital