The role of Aspartate in immune function in sepsis

Abstract Background: Sepsis carries a high risk of mortality, with immune suppression being a crucial aspect of its immunological pathophysiology. Immune cells are highly dependent on the ATP generation, nucleotide synthesis, and redox balance, in which amino acids including aspartate (ASP) play important role. Methods: We performed metabolomics and transcriptomics study using peripheral blood mononuclear cells (PBMCs) in cecal slurry model in rats. We conducted both in vivo and in vitro sepsis studies to investigate the effects of ASP on immune function. In in-vivo study, the effects of ASP were seen in terms of survival rate, bacterial clearance, acute kidney injury, and the immune response. We also used rat PBMC phagocytosis model to confirm the effects of ASP. We compared ASP level in PBMC between septic patients and healthy volunteers. Results: In metabolomics study, we found that intracellular ASP level is decreased in the status of immune suppression. Administering ASP in the animal sepsis model resulted in increased survival, less kidney injury, and improved immune function. In an in-vitro model, inhibiting ASP production induced immune suppression, partially mitigated by ASP supplementation. In septic patients, the ASP level in PBMCs was decreased. Conclusions: ASP is a key metabolite in immune function, and its deficiency is associated with immune depression, which could be reversed by ASP supplementation. Consequently, we suggest that ASP could serve as a new biomarker and therapeutic target for immune suppression in sepsis.