Mone Kiruthiga, Garcia Eloy Jose Torres, Abdullatif Fatema, Rasquinha Mahima T, Sur Meghna, Hanafy Mostafa, Zinniel Denise K, Singh Shraddha, Thomas Raymond, Barletta Raul G, Gebregiworgis Teklab, Reddy Jay
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada.
Microorganisms. 2025 Feb 22;13(3):492. doi: 10.3390/microorganisms13030492.
Freund's adjuvants have been used in vaccine and autoimmune settings, and their effects can be overlapping or unique to each. While both incomplete Freund's adjuvants (IFA) and complete Freund's adjuvants (CFA) influence antibody and T cell responses, the robust T helper 1 cytokines induced by the mycobacterial components make CFA the powerful immunostimulating adjuvant. In these studies, the adjuvant effects are investigated in a select population of cells, and the changes, if any, with the metabolic alterations in the systemic compartment are unclear. We investigated whether the effects of IFA and CFA can be influenced by the metabolic shifts in mice immunized with saline, IFA, or CFA using var. Bacillus Calmette-Guérin (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 metabolic 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 more significant perturbations in lipid and amino acid metabolism, particularly involving glycerophospholipids, cysteine, and aromatic amino acids. In contrast, comparisons between the BCG and IFA groups indicated a more pronounced disruption in central energy metabolism pathways, such as the citric acid cycle and pyruvate metabolism. Together, the data suggest that the serum metabolite profiles in response to IFA and CFA might play a role in modulating the immune responses.
弗氏佐剂已用于疫苗和自身免疫疾病的治疗中，其效果在这两种应用中可能重叠或各有独特之处。尽管不完全弗氏佐剂（IFA）和完全弗氏佐剂（CFA）都会影响抗体和T细胞反应，但分枝杆菌成分诱导产生的强大辅助性T细胞1细胞因子使CFA成为强大的免疫刺激佐剂。在这些研究中，佐剂效应是在选定的细胞群体中进行研究的，而全身代谢变化（若有）所产生的影响尚不清楚。我们使用卡介苗（BCG）变种作为阳性对照，研究了用生理盐水、IFA或CFA免疫的小鼠代谢变化是否会影响IFA和CFA的效果。免疫七天后，我们使用液相色谱结合高分辨率质谱和多变量统计分析来分析血清代谢物谱，以确定各组之间的代谢特征。数据显示，在得分空间中，与生理盐水组相比，CFA组和BCG组更为接近，而IFA组表现出中间特征。此外，CFA组和BCG组之间的比较显示，脂质和氨基酸代谢存在更显著的扰动，特别是涉及甘油磷脂、半胱氨酸和芳香族氨基酸。相比之下，BCG组和IFA组之间的比较表明，中心能量代谢途径，如柠檬酸循环和丙酮酸代谢，受到更明显的干扰。总体而言，数据表明，对IFA和CFA产生反应的血清代谢物谱可能在调节免疫反应中发挥作用。
