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Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells

Author

Listed:
  • Juraj Adamik

    (Parker Institute for Cancer Immunotherapy)

  • Paul V. Munson

    (Parker Institute for Cancer Immunotherapy)

  • Felix J. Hartmann

    (German Cancer Research Center (DKFZ))

  • Alexis J. Combes

    (University of California San Francisco
    University of California San Francisco
    CoLabs, University of California San Francisco)

  • Philippe Pierre

    (Centre d’Immunologie de Marseille-Luminy
    University of Aveiro
    Shanghai Jiao Tong University School of Medicine)

  • Matthew F. Krummel

    (University of California San Francisco
    University of California San Francisco)

  • Sean C. Bendall

    (Stanford University)

  • Rafael J. Argüello

    (Centre d’Immunologie de Marseille-Luminy)

  • Lisa H. Butterfield

    (Parker Institute for Cancer Immunotherapy
    University of California San Francisco)

Abstract

Cellular metabolism underpins immune cell functionality, yet our understanding of metabolic influences in human dendritic cell biology and their ability to orchestrate immune responses is poorly developed. Here, we map single-cell metabolic states and immune profiles of inflammatory and tolerogenic monocytic dendritic cells using recently developed multiparametric approaches. Single-cell metabolic pathway activation scores reveal simultaneous engagement of multiple metabolic pathways in distinct monocytic dendritic cell differentiation stages. GM-CSF/IL4-induce rapid reprogramming of glycolytic monocytes and transient co-activation of mitochondrial pathways followed by TLR4-dependent maturation of dendritic cells. Skewing of the mTOR:AMPK phosphorylation balance and upregulation of OXPHOS, glycolytic and fatty acid oxidation metabolism underpin metabolic hyperactivity and an immunosuppressive phenotype of tolerogenic dendritic cells, which exhibit maturation-resistance and a de-differentiated immune phenotype marked by unique immunoregulatory receptor signatures. This single-cell dataset provides important insights into metabolic pathways impacting the immune profiles of human dendritic cells.

Suggested Citation

  • Juraj Adamik & Paul V. Munson & Felix J. Hartmann & Alexis J. Combes & Philippe Pierre & Matthew F. Krummel & Sean C. Bendall & Rafael J. Argüello & Lisa H. Butterfield, 2022. "Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32849-1
    DOI: 10.1038/s41467-022-32849-1
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    1. Erika M. Palmieri & Marieli Gonzalez-Cotto & Walter A. Baseler & Luke C. Davies & Bart Ghesquière & Nunziata Maio & Christopher M. Rice & Tracey A. Rouault & Teresa Cassel & Richard M. Higashi & Andre, 2020. "Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    2. Xingrong Du & Jing Wen & Yanyan Wang & Peer W. F. Karmaus & Alireza Khatamian & Haiyan Tan & Yuxin Li & Cliff Guy & Thanh-Long M. Nguyen & Yogesh Dhungana & Geoffrey Neale & Junmin Peng & Jiyang Yu & , 2018. "Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells," Nature, Nature, vol. 558(7708), pages 141-145, June.
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