Monocyte progenitors give rise to multinucleated giant cells.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
01 04 2021
Historique:
received: 20 08 2018
accepted: 23 02 2021
entrez: 2 4 2021
pubmed: 3 4 2021
medline: 20 4 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33795674
doi: 10.1038/s41467-021-22103-5
pii: 10.1038/s41467-021-22103-5
pmc: PMC8016882
doi:

Substances chimiques

Cytokines 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2027

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Auteurs

Anne Kathrin Lösslein (AK)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
MOTI-VATE Graduate School, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Florens Lohrmann (F)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Center for Pediatrics and Adolescent Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Spemann Graduate School for Biology and Medicine (SGBM) and IMM-PACT Clinician Scientist Program, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Lisa Scheuermann (L)

Max Planck Institute for Infection Biology, Berlin, Germany.

Kourosh Gharun (K)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Faculty of Biology, University of Freiburg, Freiburg, Germany.

Jana Neuber (J)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Faculty of Biology, University of Freiburg, Freiburg, Germany.

Julia Kolter (J)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Aaron James Forde (AJ)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Faculty of Biology, University of Freiburg, Freiburg, Germany.

Christian Kleimeyer (C)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Ying Yee Poh (YY)

Nanyang Technological University, Lee Kong Chian School of Medicine, Singapore, Singapore.

Matthias Mack (M)

University Hospital Regensburg, Internal Medicine II, Nephrology, Regensburg, Germany.

Antigoni Triantafyllopoulou (A)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
German Rheumatism Research Centre Berlin, Leibniz Association, Berlin, Germany.

Micah D Dunlap (MD)

Department of Molecular Microbiology, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.

Shabaana A Khader (SA)

Department of Molecular Microbiology, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.

Maximilian Seidl (M)

Center for Chronic Immunodeficiency and Institute for Clinical Pathology, Department of Pathology, Medical Center and Faculty of Medicine, Freiburg, Germany and Institute of Pathology, Heinrich Heine University and University Hospital of Duesseldorf, Duesseldorf, Germany.

Alexandra Hölscher (A)

Forschungszentrum Borstel, Leibniz Lungenzentrum, Borstel, Germany.

Christoph Hölscher (C)

Forschungszentrum Borstel, Leibniz Lungenzentrum, Borstel, Germany.
Deutsches Zentrum für Infektionsforschung, Standort Borstel, Borstel, Germany.

Xue Li Guan (XL)

Nanyang Technological University, Lee Kong Chian School of Medicine, Singapore, Singapore.

Anca Dorhoi (A)

Max Planck Institute for Infection Biology, Berlin, Germany.
Institute of Immunology, Federal Research Institute for Animal Health, Friedrich-Loeffler-Institut (FLI), Insel Riems, Germany.
Faculty of Mathematics and Natural Sciences, University of Greifswald, Greifswald, Germany.

Philipp Henneke (P)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany. Philipp.henneke@uniklinik-freiburg.de.
Center for Pediatrics and Adolescent Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany. Philipp.henneke@uniklinik-freiburg.de.

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Classifications MeSH