Monocyte progenitors give rise to multinucleated giant cells

Anne Kathrin Lösslein, Florens Lohrmann, Lisa Scheuermann, Kourosh Gharun, Jana Neuber, Julia Kolter, Aaron James Forde, Christian Kleimeyer, Ying Yee Poh, Matthias Mack, Antigoni Triantafyllopoulou, Micah D. Dunlap, Shabaana A. Khader, Maximilian Seidl, Alexandra Hölscher, Christoph Hölscher, Xue Li Guan, Anca Dorhoi and Philipp Henneke ()
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Anne Kathrin Lösslein: University of Freiburg
Florens Lohrmann: University of Freiburg
Lisa Scheuermann: Max Planck Institute for Infection Biology
Kourosh Gharun: University of Freiburg
Jana Neuber: University of Freiburg
Julia Kolter: University of Freiburg
Aaron James Forde: University of Freiburg
Christian Kleimeyer: University of Freiburg
Ying Yee Poh: Nanyang Technological University, Lee Kong Chian School of Medicine
Matthias Mack: University Hospital Regensburg, Internal Medicine II, Nephrology
Antigoni Triantafyllopoulou: University of Freiburg
Micah D. Dunlap: Washington University in St. Louis School of Medicine
Shabaana A. Khader: Washington University in St. Louis School of Medicine
Maximilian Seidl: Heinrich Heine University and University Hospital of Duesseldorf
Alexandra Hölscher: Forschungszentrum Borstel, Leibniz Lungenzentrum
Christoph Hölscher: Forschungszentrum Borstel, Leibniz Lungenzentrum
Xue Li Guan: Nanyang Technological University, Lee Kong Chian School of Medicine
Anca Dorhoi: Max Planck Institute for Infection Biology
Philipp Henneke: University of Freiburg

Nature Communications, 2021, vol. 12, issue 1, 1-22

Abstract: Abstract The immune response to mycobacteria is characterized by granuloma formation, which features multinucleated giant cells as a unique macrophage type. We previously found that multinucleated giant cells result from Toll-like receptor-induced DNA damage and cell autonomous cell cycle modifications. However, the giant cell progenitor identity remained unclear. Here, we show that the giant cell-forming potential is a particular trait of monocyte progenitors. Common monocyte progenitors potently produce cytokines in response to mycobacteria and their immune-active molecules. In addition, common monocyte progenitors accumulate cholesterol and lipids, which are prerequisites for giant cell transformation. Inducible monocyte progenitors are so far undescribed circulating common monocyte progenitor descendants with high giant cell-forming potential. Monocyte progenitors are induced in mycobacterial infections and localize to granulomas. Accordingly, they exhibit important immunological functions in mycobacterial infections. Moreover, their signature trait of high cholesterol metabolism may be piggy-backed by mycobacteria to create a permissive niche.

Date: 2021
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DOI: 10.1038/s41467-021-22103-5

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