Neutrophil heterogeneity in complement C1q expression associated with sepsis mortality

Area of Science:

• Immunology
• Critical Care Medicine
• Molecular Biology

Background:

• Sepsis is a major global health threat with high mortality.
• Understanding sepsis mortality predictors is crucial for improved patient outcomes.
• Current prognostic measures for sepsis are limited, hindering effective clinical management.

Purpose of the Study:

• To identify novel prognostic biomarkers for septic mortality.
• To explore the role of neutrophil complement component 1q (C1q) in sepsis.
• To investigate C1q as a potential therapeutic target for sepsis.

Main Methods:

• Analysis of neutrophil CD49c expression and C1q gene expression in sepsis patients.
• Measurement of neutrophil C1q protein levels in septic survivors and non-survivors.
• In vivo studies using mouse sepsis models with C1q blockade or knockout.
• Evaluation of C1q administration as a therapeutic intervention in mouse sepsis models.

Main Results:

• A distinct neutrophil subpopulation with high CD49c and C1q expression emerges in severe sepsis.
• Septic patients who died had significantly lower neutrophil C1q protein levels compared to survivors.
• Blocking or deleting neutrophil C1q in mice exacerbated sepsis mortality.
• Administration of C1q to septic mice significantly improved survival rates.

Conclusions:

• Neutrophil C1q is a reliable prognostic biomarker for sepsis mortality.
• Neutrophil C1q plays a protective role in sepsis, potentially by facilitating the clearance of apoptotic neutrophils.
• Neutrophil C1q represents a promising novel therapeutic target for sepsis treatment.