Dataset Information

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

ABSTRACT: 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.

ORGANISM(S): Papio ursinus

PROVIDER: GSE221652 | GEO | 2023/06/12

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Sepsis remains a leading cause of death and currently has no pathogenesis-specific therapy. Hampered progress is partly due to the lack of insight into deep mechanistic processes. Deciphering the functions of microRNAs in sepsis pathogeny became a dynamic research topic in the last decade. To screen for new microRNA targets for sepsis therapeutics, we used human samples: microRNA array data from peripheral blood mononuclear cells (PBMCs) from sepsis patients and controls, whole blood samples from sepsis survivors; and multiple animal models: mouse cecum ligation-puncture (CLP)-induced sepsis, mouse viral microRNA challenge, and baboon Gram-positive and Gram-negative sepsis models. miR-93-5p met the criteria for a therapeutic target, being overexpressed in baboons which died early after induction of sepsis and downregulated in humans who survived after sepsis. Therapeutically, inhibiting miR-93-5p prolonged the overall survival of mice with CLP-induced sepsis, with a stronger effect in old mice. Mechanistically, anti-miR-93-5p therapy reduced inflammatory monocytes and increased circulating effector memory T cells, especially CD4+ subset. Ago2-immunoprecipitation in miR-93-knockout T cells identified important regulatory receptors, CD28 and CD160, as direct miR-93-5p target genes. In conclusion, miR-93-5p is a potential therapeutic target in sepsis in the elderly through its regulation of both innate and adaptive immunity. We applied the Ago2-RIP Chip (Ribonucleoprotein ImmunoPrecipitation followed by microarray analysis) to identify miR-93-5p target mRNAs. This methodology uses beads coupled to either anti-Ago2 antibody (or an IgG control) to pull down the RISC complex together with any miRNA-interacting mRNAs. To define target genes of miR-93-5p, we assessed mRNA transcripts enriched in the Ago2-IP fraction of JURKAT parental cells or control cells (where miR-93-5p is present) but not in the two KO clones (where miR-93-5p is absent) by microarray

Dataset Information

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

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets