Understanding the Relationship Between Immune Cells and Sepsis Through Mendelian Randomization and Single-Cell Transcriptome Analysis

Background: Sepsis is a condition characterized by an immune system imbalance, leading to high rates of morbidity and mortality. Although immune cells have the ability to eliminate infection, they can also cause tissue damage. Therefore, understanding the role of different immune cells in sepsis is crucial for effective treatment. Purpose: The goal of this research is to examine the correlation between sepsis and immune cells, as well as their specific traits, through the utilization of Mendelian randomization (MR) analysis and single-cell transcriptome analysis. Method: To investigate the causal association between immune cell signals and the susceptibility to sepsis, we conducted a comprehensive two-sample MR analysis utilizing publicly accessible genetic data. The analysis focused on four types of immune signals: median fluorescence intensity (MFI), relative cell number (RC), absolute cell number (AC), and morphological parameters (MP). Additionally, single-cell transcriptome sequencing data analysis techniques were used to explore the characteristics of immune cells in sepsis. Result: After correcting for multiple testing, there was no statistically significant impact of sepsis on immune phenotype. However, our research findings support the notion that the FSC-A parameter on the HLA DR ⁺ natural killer immune cell phenotype has a protective effect against sepsis. Furthermore, analysis of single-cell RNA sequencing data revealed a significant increase in the S100A8+S100A9+ neutrophil subpopulation in sepsis, while the proportion of T cells was significantly lower compared to healthy controls. Conclusion: Our results suggest that HLA DR ⁺ natural killer cells have a significant protective effect on sepsis. Additionally, the S100A8+S100A9+ neutrophil subpopulation is significantly increased in sepsis.