Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis.

Area of Science:

• Immunology
• Critical Care Medicine
• Epigenetics

Background:

• Sepsis presents a global health challenge, significantly contributing to patient morbidity and mortality.
• Elevated circulating myeloid-derived suppressor cells (MDSCs) are a hallmark of the host immune response to sepsis and correlate with poor outcomes.
• MDSCs are plastic and susceptible to modification, suggesting potential for epigenetic interventions.

Purpose of the Study:

• To investigate the evolution of the suppressive phenotype of MDSCs in surgical ICU patients post-sepsis.
• To identify epigenetic differences in MDSCs that may underlie observed functional changes.

Main Methods:

• Phenotyping of circulating MDSCs from 267 surgical sepsis survivors over six weeks.
• Co-culture of enriched MDSCs with autologous T cells to assess suppressive function.
• Analysis of microRNA expression in enriched MDSCs.

Main Results:

• MDSC numbers remained elevated for at least six weeks post-sepsis.
• MDSCs from 14 days onward post-sepsis significantly suppressed T cell proliferation and IL-2 production.
• These later-stage MDSCs exhibited distinct miRNA expression patterns compared to earlier time points.

Conclusions:

• In sepsis survivors, increased immature myeloid cells exhibit delayed development of immune suppressive function.
• This functional maturation of MDSCs is associated with a specific epigenome, particularly miRNA expression.
• These findings offer insights into the mechanisms of chronic immune suppression following sepsis.