Nano-Emulsion Adjuvant Enhances Cross-presentation by Lipid Body Formation Independent of Glycolysis
Suresh, M.; Lee, W.; Kingstad-Bakke, B.; Paulson, B.; Larsen, A.; Overmyer, K.; Marinaik, C.; Dull, K.; Toy, R.; Vogel, G.; Mueller, K.; Tweed, K.; Walsh, A.; Russell, J.; Saha, K.; Reyes, L.; Skala, M.; Sauer, J.-D.; Shayakhmetov, D. M.; Coon, J.; Roy, K.
Show abstract
Here, we report that a carbomer-based adjuvant, Adjuplex(R) (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.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Macrophage Innate Training Induced by IL-4 and IL-13 Activation Enhances OXPHOS Driven Anti-Mycobacterial Responses 95%
- Bmal1 integrates mitochondrial metabolism and macrophage activation 95%
- Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the immunoreceptor CD300a 95%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Intracellular Galectin-9 controls dendritic cell function by maintaining plasma membrane rigidity 95%
- Healthy cells functionally present TAP-independent SSR1 peptides: implications for selection of clinically relevant antigens 93%
- The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.