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Updated: Feb 28, 2026
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Profiling of human and microbial cell-free DNA reflects early host-pathogen interactions in sepsis
Katharina Hoeter1, Elmo W I Neuberger2, Linda Marriott3
1Department of Anesthesiology, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.
Objectives:
In sepsis, circulating cell-free DNA (cfDNA) originates from host cells (damage-associated molecular patterns, DAMPs) and pathogens (pathogen-associated molecular patterns, PAMPs), contributing to immune activation and offering potential as both a biomarker and a therapeutic target. While DAMPs are thought to predominate in early sepsis, this study aimed to quantify their relative abundance and assess their correlation with inflammatory markers compared to PAMPs.
Methods:
In this prospective observational study, blood samples of 18 ICU patients were collected within 24 hours of sepsis diagnosis. Plasma cfDNA was analyzed via qPCR (targeting human LINE-1) and iSEP-SEQ nanopore sequencing. Human and microbial cfDNA were quantified, and method correlation was assessed using Kendall's tau-b correlation. Associations with inflammatory biomarkers were tested using Spearman correlation analysis and group comparisons between human and non-human reads were analyzed with Pearson correlation analysis. The study received ethical approval from the Landesärztekammer Rheinland-Pfalz (Approval Number: 2020-15535).
Results:
cfDNA was predominantly of human origin, comprising 99.86% of classified reads, with microbial cfDNA accounting for only 0.077% (p < 0.001). qPCR-based cfDNA concentrations strongly correlated with human read counts from sequencing (τ = 0.712; p < 0.001). Human cfDNA levels were significantly associated with LDH, WBC, and CRP. Microbial cfDNA, although low in abundance, correlated with WBC, CRP, and D-dimer.
Conclusions:
In early sepsis, human cfDNA is markedly more abundant than microbial cfDNA. However, both exhibit strong correlations with inflammatory and tissue injury markers. These findings support a model of PAMP-triggered and DAMP-driven inflammation and identify human cfDNA as a promising biomarker and potential therapeutic target.
Clinical Trial Registration:
https://drks.de/search/de/trial/DRKS00025222/details, identifier DRKS-ID: 00025222.
Insights
In early sepsis, human cell-free DNA (cfDNA) is far more abundant than microbial cfDNA. Both human and microbial cfDNA correlate with inflammatory markers, suggesting cfDNA is a promising biomarker.
Area of Science:
- Sepsis research
- Molecular diagnostics
- Immunology
Background:
- Circulating cell-free DNA (cfDNA) in sepsis originates from host (DAMPs) and pathogens (PAMPs).
- DAMPs are hypothesized to dominate early sepsis, influencing immune activation.
- cfDNA presents potential as a sepsis biomarker and therapeutic target.
Purpose of the Study:
- Quantify the relative abundance of human (DAMPs) and microbial (PAMPs) cfDNA in early sepsis.
- Assess the correlation of cfDNA abundance with key inflammatory markers.
- Investigate cfDNA's role in sepsis-related immune responses.
Main Methods:
- Prospective observational study of 18 ICU patients within 24 hours of sepsis diagnosis.
- Plasma cfDNA analysis using qPCR (LINE-1) and nanopore sequencing (iSEP-SEQ).
- Quantification of human and microbial cfDNA, with correlation analysis against inflammatory biomarkers (LDH, WBC, CRP, D-dimer).
Main Results:
- cfDNA was predominantly of human origin (99.86%), with microbial cfDNA at 0.077% (p < 0.001).
- qPCR cfDNA concentrations strongly correlated with human cfDNA sequencing counts (τ = 0.712; p < 0.001).
- Human cfDNA associated with LDH, WBC, and CRP; microbial cfDNA correlated with WBC, CRP, and D-dimer.
Conclusions:
- Human cfDNA significantly outweighs microbial cfDNA in early sepsis.
- Both human and microbial cfDNA fractions correlate with inflammatory and tissue injury markers.
- Findings support a DAMP-driven inflammation model and highlight human cfDNA as a key biomarker.
