Extensive Changes in Transcriptomic "Fingerprints" and Immunological Cells in the Large Organs of Patients Dying of Acute Septic Shock and Multiple Organ Failure Caused by Neisseria meningitidis.

Frontiers in Cellular and Infection Microbiology
Berit Sletbakk BruslettoReidun Øvstebø

Abstract

Background: Patients developing meningococcal septic shock reveal levels of Neisseria meningitidis (106-108/mL) and endotoxin (101-103 EU/mL) in the circulation and organs, leading to acute cardiovascular, pulmonary and renal failure, coagulopathy and a high case fatality rate within 24 h. Objective: To investigate transcriptional profiles in heart, lungs, kidneys, liver, and spleen and immunostain key inflammatory cells and proteins in post mortem formalin-fixed, paraffin-embedded (FFPE) tissue samples from meningococcal septic shock patients. Patients and Methods: Total RNA was isolated from FFPE and fresh frozen (FF) tissue samples from five patients and two controls (acute non-infectious death). Differential expression of genes was detected using Affymetrix microarray analysis. Lung and heart tissue samples were immunostained for T-and B cells, macrophages, neutrophils and the inflammatory markers PAI-1 and MCP-1. Inflammatory mediators were quantified in lysates from FF tissues. Results: The transcriptional profiles showed a complex pattern of protein-coding and non-coding RNAs with significant regulation of pathways associated with organismal death, cell death and survival, leukocyte migration, cellular movement, prolifer...Continue Reading

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Datasets Mentioned

BETA
GSE141864

Methods Mentioned

BETA
Reverse Transcription PCR
PCA
PLAT
PCR

Software Mentioned

[UNK]
IPA
Partek Genomics Suite
GraphPad Prism
Ingenuity
Molecular Activity Predictor
Partek® Genomics [UNK]
Ingenuity Pathways Analysis ( IPA )
GraphPad
AGCC (

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