Metabolic reprogramming in response to adjuvants 3332

Abstract Description Adjuvants can influence immune responses through metabolic reprogramming that can promote or break self-tolerance. It is well known that self-antigens administered in incomplete Freund’s adjuvant (IFA) favors tolerance and expansion of Treg cells, whereas complete Freund’s adjuvant (CFA) containing the mycobacterial antigens promotes T cell responses. We investigated whether the effects of IFA and CFA can be influenced by their metabolic shifts in A/J mice immunized with saline, IFA or CFA using BCG as a positive control. After seven days of immunization, we analyzed the serum metabolite profiles using liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to identify spectral features between the groups. The data revealed that, in the scores space, the CFA and BCG groups were more closely aligned compared to the saline group, while the IFA group displayed an intermediate profile. Furthermore, comparisons between the CFA and BCG groups showed greater perturbations in lipid metabolism and amino acid metabolism, particularly involving cysteine and aromatic amino acids. In contrast, comparisons between the BCG and IFA groups indicated a more pronounced disruptions in central energy metabolism pathways, such as the citric acid cycle and pyruvate metabolism. Together, the data suggest the serum metabolite profiles in response to IFA and CFA might play a role in modulating the immune responses. Funding Sources NIH R21AI166773 Topic Categories Basic Autoimmunity (BA)