Anti-miR-93-5p therapy prolongs sepsis survival by restoring the peripheral immune response

Escherichia coli and Staphylococcus are among the most common causes of bacterial sepsis, a deadly syndrome characterized by uncontrolled activation of coagulation and complement enzymatic cascades an exaggerated immune response. We performed in vivo experimental sepsis in baboons to characterize the host response to bacterial infection in blood cells. We demonstrate that bacterial infection leads to early induction of proinflammatory genes followed by a delayed activation of anti-inflammatory pathways. In addition, we observe changes in genes and pathways associated coagulation and complement as well as with leukocyte adhesion, migration and cell death. Our study provides important insights into the temporal kinetics of gene expression in leukocytes during bacterial sepsis. Overall design: Characterization of gene expression changes in blood leuckocytes during the time course of sepsis progression in baboons mRNA profiling of blood leukocytes from baboons challenged with lethal doses (1-3x10E10 colony forming units) Gram negative (E. coli) and Gram positive (S. aureus) bacteria, as a function of time before sepsis (0 hours) versus post-infection (2, 4, 8, 24 hours )