Radiotherapy induces persistent innate immune reprogramming of microglia into a primed state.

CP: Cancer CP: Immunology brain tumor innate immune memory microglia microglial priming neuroinflammation radiotherapy

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
14 Feb 2024
Historique:
received: 16 05 2023
revised: 06 12 2023
accepted: 25 01 2024
medline: 15 2 2024
pubmed: 15 2 2024
entrez: 15 2 2024
Statut: aheadofprint

Résumé

Over half of patients with brain tumors experience debilitating and often progressive cognitive decline after radiotherapy treatment. Microglia, the resident macrophages in the brain, have been implicated in this decline. In response to various insults, microglia can develop innate immune memory (IIM), which can either enhance (priming or training) or repress (tolerance) the response to subsequent inflammatory challenges. Here, we investigate whether radiation affects the IIM of microglia by irradiating the brains of rats and later exposing them to a secondary inflammatory stimulus. Comparative transcriptomic profiling and protein validation of microglia isolated from irradiated rats show a stronger immune response to a secondary inflammatory insult, demonstrating that radiation can lead to long-lasting molecular reprogramming of microglia. Transcriptomic analysis of postmortem normal-appearing non-tumor brain tissue of patients with glioblastoma indicates that radiation-induced microglial priming is likely conserved in humans. Targeting microglial priming or avoiding further inflammatory insults could decrease radiotherapy-induced neurotoxicity.

Identifiants

DOI: 10.1016/j.celrep.2024.113764 PMID: 38358885
pubmed: 38358885
pii: S2211-1247(24)00092-5
doi: 10.1016/j.celrep.2024.113764
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113764

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests L.B. received funding from Ion Beam Applications (IBA) as part of the ZonMw Off-Road program; however, the company did not have any input and interpretation on the experiment design and data.

Auteurs

Daniëlle C Voshart (DC)

Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Takuya Oshima (T)

Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.

Yuting Jiang (Y)

Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Gideon P van der Linden (GP)

Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Anna P Ainslie (AP)

Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands; European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.

Luiza Reali Nazario (L)

Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Fleur van Buuren-Broek (F)

Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Ayla C Scholma (AC)

Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Hilmar R J van Weering (HRJ)

Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.

Nieske Brouwer (N)

Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.

Jeffrey Sewdihal (J)

Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Uilke Brouwer (U)

Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Rob P Coppes (RP)

Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Inge R Holtman (IR)

Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.

Bart J L Eggen (BJL)

Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.

Susanne M Kooistra (SM)

Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.

Lara Barazzuol (L)

Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands. Electronic address: l.barazzuol@umcg.nl.

Classifications MeSH