Pathogen-specific host response in critically ill patients with blood stream infections: a nested case-control study

Area of Science:

• * Molecular biology
• * Immunology
• * Critical care medicine

Background:

• * Host response to infection is highly variable.
• * Limited understanding of pathogen-specific contributions to this heterogeneity.
• * Focus on critically ill patients with bloodstream infections (BSI).

Purpose of the Study:

• * To compare host responses in critically ill patients with BSI.
• * To determine the extent to which the causative pathogen explains host response variation.
• * To identify pathogen-specific host response signatures.

Main Methods:

• * RNA sequencing and microarray analysis of blood samples from 341 patients.
• * Differential gene expression and pathway analyses.
• * Development and validation of transcriptome classifiers for pathogen-specific BSIs.
• * Measurement of 20 plasma biomarkers.

Main Results:

• * The causative pathogen explained 41.8% of blood transcriptomic variance in BSI patients.
• * Distinct host response patterns were observed for different bacterial species (e.g., Streptococcus, Staphylococcus aureus, Escherichia coli).
• * Streptococcus BSI showed the strongest immune activation; E. coli BSI showed the strongest systemic inflammation; S. aureus BSI showed the strongest endothelial activation.

Conclusions:

• * The causative pathogen is a major driver of host response heterogeneity in BSI.
• * Pathogen-specific host response profiles can be identified.
• * Findings have implications for understanding and potentially tailoring treatments for BSI.