Circulating cell-free DNA indicates M1/M2 responses during septic peritonitis

Area of Science:

• Immunology
• Molecular Biology
• Pathophysiology

Background:

• Circulating cell-free DNA (cfDNA) is a potential biomarker in diseases like sepsis.
• Tissue damage in sepsis is linked to cell lysis, necrosis, and apoptosis, releasing cfDNA.
• Macrophage polarization (M1 for killing, M2 for repair) is crucial in sepsis-induced tissue damage, but its relationship with cfDNA is unexplored.

Purpose of the Study:

• To investigate the correlation between cfDNA levels and M1/M2 macrophage responses in a mouse model of septic peritonitis.
• To determine if cfDNA can serve as an indicator of the balance between pro-inflammatory (M1) and pro-resolving (M2) immune responses during sepsis.

Main Methods:

• Utilized a bacterial injection-induced septic peritonitis mouse model using C57bl/6 (M1-dominant) and Balb/c (M2-dominant) strains.
• Quantified cfDNA levels in peripheral blood.
• Assessed M1/M2 related cytokines, including tumor necrosis factor α (TNFα) and interleukin 10 (IL-10).
• Monitored peripheral blood monocyte subtypes (Ly6C(high) and Ly6C(low)) to represent M1 and M2 populations, respectively.

Main Results:

• M2-dominant Balb/c mice exhibited better septic peritonitis prognosis with lower cfDNA levels compared to M1-dominant C57bl/6 mice.
• Balb/c mice showed lower TNFα and higher IL-10 production than C57bl/6 mice.
• C57bl/6 mice displayed a higher proportion of inflammatory Ly6C(high) monocytes (M1-like) than Balb/c mice.
• cfDNA levels strongly correlated with the ratio of Ly6C(high) to Ly6C(low) monocytes, reflecting M1/M2 balance.

Conclusions:

• cfDNA levels are significantly associated with the M1/M2 macrophage response balance during septic peritonitis.
• cfDNA serves as a valuable indicator for assessing the M1/M2 (killing/healing) immune status in sepsis.
• The findings highlight cfDNA's potential as a biomarker for predicting sepsis outcomes based on immune polarization.