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Environmental stimuli shape microglial plasticity in glioma

by Kaminska, Bozena , Di Angelantonio, Silvia , Tremblay, Marie-Eve , Basilico, Bernadette , Limatola, Cristina , Esposito, Vincenzo , Santoni, Angela , Savage, Julie , Garofalo, Stefano , Seyfried, Thomas , Mieczkowski, Jakub , Porzia, Alessandra , Stepniak, Karolina , Maggio, Roberta , Chece, Giuseppina , Cortese, Barbara , Bisht, Kanchan , Cignitti, Giorgio , Bernardini, Giovanni , Pagani, Francesca , Mainiero, Fabrizio

in Brain cancer / Brain tumors / Brain-derived neurotrophic factor / CD11b antigen / Cell growth / Chemokines / Cytokines / enriched environment / Enrichment / Environmental effects / Gene expression / Genotype & phenotype / Glioma / Immunosuppression / Inflammation / Interferon / Interleukin 15 / Investigations / Kinases / Laboratories / Macrophages / Medical prognosis / Microglia / mouse model / Myeloid cells / Natural killer cells / Neuroscience / Neurosciences / NK cells / Phagocytes / Phenotypes / Physiology / Software / γ-Interferon

2017

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2017

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2017

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Journal Article

Environmental stimuli shape microglial plasticity in glioma

Kaminska, Bozena,

Di Angelantonio, Silvia,

Tremblay, Marie-Eve,

Basilico, Bernadette,

Limatola, Cristina,

Esposito, Vincenzo,

Santoni, Angela,

Savage, Julie,

Garofalo, Stefano,

Seyfried, Thomas,

Mieczkowski, Jakub,

Porzia, Alessandra,

Stepniak, Karolina,

Maggio, Roberta,

Chece, Giuseppina,

Cortese, Barbara,

Bisht, Kanchan,

Cignitti, Giorgio,

Bernardini, Giovanni,

Pagani, Francesca,

Mainiero, Fabrizio

2017

Overview

In glioma, microglia and infiltrating macrophages are exposed to factors that force them to produce cytokines and chemokines, which contribute to tumor growth and to maintaining a pro-tumorigenic, immunosuppressed microenvironment. We demonstrate that housing glioma-bearing mice in enriched environment (EE) reverts the immunosuppressive phenotype of infiltrating myeloid cells, by modulating inflammatory gene expression. Under these conditions, the branching and patrolling activity of myeloid cells is increased, and their phagocytic activity is promoted. Modulation of gene expression depends on interferon-(IFN)-γ produced by natural killer (NK) cells. This modulation disappears in mice depleted of NK cells or lacking IFN-γ, and was mimicked by exogenous interleukin-15 (IL-15). Further, we describe a key role for brain-derived neurotrophic factor (BDNF) that is produced in the brain of mice housed in EE, in mediating the expression of IL-15 in CD11b cells. These data define novel mechanisms linking environmental cues to the acquisition of a pro-inflammatory, anti-tumor microenvironment in mouse brain.

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Publisher

eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd

Subject

Brain cancer

/ Brain tumors

/ Brain-derived neurotrophic factor