Nano-Emulsion Adjuvant Enhances Cross-presentation by Lipid Body Formation Independent of Glycolysis

• Published in: bioRxiv
• Main Authors: Suresh, M, Lee, Woojong, Kingstad-Bakke, Brock, Paulson, Brett, Larsen, Autumn, Overmyer, Katherine, Marinaik, Chandranaik, Dull, Kelly, Toy, Randall, Vogel, Gabriela, Mueller, Katherine, Tweed, Kelsey, Walsh, Alex, Russell, Jason, Saha, Krishanu, Reyes, Leticia, Skala, Melissa, John-Demian Sauer, Shayakhmetov, Dmitry M, Coon, Joshua, Roy, Krishnendu
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 12.05.2020
• Subjects: Adjuvants; Antigen presentation; Antigens; Caspase-1; CD8 antigen; Cell-mediated immunity; Glycolysis; Intracellular; Lipid bodies; Lymphocytes T; Metabolism; Oxidative phosphorylation; Phosphorylation
• DOI: 10.1101/2020.05.08.083790

Here, we report that a carbomer-based adjuvant, Adjuplex® (ADJ), stimulated robust CD8 T-cell responses to subunit antigens by modulating multiple steps in the cytosolic pathway of cross-presentation, and afforded effective immunity against virus and intracellular bacteria. Cross-presentation induced by TLR agonists requires a critical switch to anabolic metabolism, but ADJ enhanced cross presentation without this metabolic switch in DCs and NLRP3-driven caspase 1 activity. Instead, ADJ induced in DCs, an unique metabolic state, typified by dampened oxidative phosphorylation and basal levels of glycolysis. In the absence of increased glycolytic flux, induction of ROS and lipid bodies (LBs) and alterations in LB composition mediated by ADJ were critical for DC cross-presentation. These findings challenge the prevailing metabolic paradigm by suggesting that DCs can perform effective DC cross-presentation, independent of glycolysis to induce robust T cell-dependent protective immunity to intracellular pathogens. These findings have implications in the rational development of novel adjuvants that promote cross-presentation and elicit potent cell-mediated immunity.