A road map from single-cell transcriptome to patient classification for the immune response to trauma

Area of Science:

• Immunology
• Genomics
• Trauma Research

Background:

• Immune dysfunction significantly impacts trauma outcomes but lacks detailed cellular understanding.
• Understanding the cellular basis of trauma-induced immune responses is crucial for improving patient care.

Purpose of the Study:

• To investigate the cellular and molecular changes in the immune system following trauma.
• To identify distinct immune response patterns in trauma patients and their clinical implications.

Main Methods:

• Single-cell RNA sequencing was performed on mononuclear cells from injured mice and trauma patients.
• Gene expression patterns in monocytes were analyzed to identify key changes and transcription factors.
• Human CD14+ monocyte signatures were defined to classify trauma patient subtypes.

Main Results:

• Trauma induced significant gene expression alterations in monocytes, traceable to myeloid progenitors in mice.
• These monocyte changes were recapitulated in human trauma patients, defining two subtypes (SG1 and SG2).
• SG1 patients showed poorer recovery, increased organ dysfunction, and higher complication rates compared to SG2.

Conclusions:

• Distinct monocyte gene expression signatures define trauma patient subtypes with different clinical trajectories.
• The identified immune response patterns are conserved across critical illnesses like trauma, burns, and sepsis.
• These findings provide a foundation for further research into immune responses in critical illness and inflammatory diseases.