Immune Mediators in Trauma Plasma Drive Specific Pathway Activation in Healthy PBMCs 4843

Abstract Description Introduction Immune response to trauma is characterized by systemic inflammation and subsequent immunosuppression. The central role of peripheral blood mononuclear cells (PBMCs) in this dynamic remains incompletely characterized. This study aims to elucidate ex-vivo immune pathway alterations in PBMCs exposed to trauma plasma compared to culture media alone. Methods Trauma plasma was collected from a cohort of polytrauma patients (n = 4) with blunt injury. PBMCs isolated from a healthy donor were cultured with 20% trauma plasma or culture media for 3 hours. RNA extracted from PBMCs was subjected to bulk RNA sequencing. Transcriptomic analysis was performed to identify differentially expressed genes (DEGs) and pathways. Upregulated pathways were identified using Ingenuity Pathway Analysis. Results 844 DEGs were identified (FDR=0.05), with 642 upregulated and 202 downregulated genes in response to trauma plasma. Key activated pathways included T-cell receptor signaling, neutrophil extracellular trap signaling, Th1 pathway, and macrophage alternative activation signaling. In contrast, culture media induced minimal immune activation, underscoring the immune-stimulatory effect of trauma plasma. Conclusions Trauma plasma induces robust immune activation in healthy PBMCs, underscoring the role of soluble factors in trauma-associated immune dysregulation. These findings highlight the therapeutic potential of targeting these pathways to modulate immune responses in trauma patients. Topic Categories Computational and Systems Immunology (COMP)