Carbomer-based Nano-Emulsion Adjuvant Enhances Dendritic Cell Cross-presentation via Lipid Body Formation Independent of Glycolysis

Year: 2020

Type: preprint

Abstract: Summary 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.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.1101/2020.05.08.083790

Institutions: University of Wisconsin–Madison, Morgridge Institute for Research, Georgia Institute of Technology, The Wallace H. Coulter Department of Biomedical Engineering, Wisconsin Institutes for Discovery, Emory University

Language: English

Topic: Immunotherapy and Immune Responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Science Foundation, American Heart Association, Emory University, National Institutes of Health, Division of Chemical, Bioengineering, Environmental, and Transport Systems

OpenAlex ID: W3022754229