Monocyte progenitors give rise to multinucleated giant cells

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

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Nature communications. - 12 (2021) , 2027, ISSN: 2041-1723

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2021
Creator
Lößlein, Anne
Lohrmann, Florens
Scheuermann, Lisa
Gharun, Kourosh
Neuber, Jana
Kolter, Julia
Forde, Aaron James
Kleimeyer, Christian
Poh, Ying Yee
Mack, Matthias
Triantafyllopoulou, Antigoni
Dunlap, Micah D.
Khader, Shabaana A.
Seidl, Maximilian
Hölscher, Alexandra
Hölscher, Christoph
Guan, Xue Li
Dorhoi, Anca
Henneke, Philipp

DOI
10.1038/s41467-021-22103-5
URN
urn:nbn:de:bsz:25-freidok-1947265
Rights
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Last update
25.03.2025, 1:54 PM CET

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Associated

Time of origin

  • 2021

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