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Published on: April 29, 2015
Circulating cell-free DNA indicates M1/M2 responses during septic peritonitis
Yi Xin1, Xingjuan Gao2, Wenxiao Wang2
1Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, PR China; Department of Pediatrics, Yuhuangding Hospital of Yantai, Yantai 264000, PR China.
Abstract:
Circulating cell-free DNA (cfDNA) has been widely suggested as clinical indicator in diseases, including sepsis. It was thought that the cfDNA was coming from the cell lysis, necrosis and apoptosis caused by tissue damages during sepsis. M1 or M2 macrophage-type responses kill or repair in vivo, which is highly relevant with the tissue damages in sepsis. The correlation between cfDNA and M1/M2 responses during sepsis was never investigated. Here, we used bacteria injection induced septic peritonitis mouse model in both M1-dominant C57bl/6 and M2-dominant Balb/c mouse strains. We found that M2-dominant Balb/c mice showed better prognosis of septic peritonitis than C57bl/6 mice, which is corresponded with lower level of cfDNA in septic Balb/c mice compared to septic C57bl/6 mice. By assessing the M1 and M2 related cytokines in both septic Balb/c and C57bl/6 mice, we found out that Balb/c mice has lower tumor necrosis factor α (TNFα) and higher interleukin 10 (IL-10) productions than C57bl/6 mice during septic peritonitis. Especially, when monitoring the monocyte subtypes in peripheral blood of these septic mice, we found out that C57bl/6 showed higher inflammatory (Ly6C(high)) monocyte (corresponding to M1 macrophage) proportion than Balb/c mice. Interestingly, we find out that cfDNA is highly correlated with the ratio of Ly6C(high) monocytes versus Ly6C(low) monocytes, which represents M1/M2 (killing/healing) responses. Our study suggested that the cfDNA is a good indicator for evaluating M1/M2 responses in septic peritonitis.
Insights
Circulating cell-free DNA (cfDNA) levels correlate with macrophage responses in sepsis. Lower cfDNA indicates a better prognosis, reflecting a shift towards healing (M2) over damaging (M1) immune responses.
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.
