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, Philipp Henneke

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Article number2027
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 1 2021

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