In glioma, microglia and infiltrating macrophages are exposed to factors that force them to produce cytokines and chemokines, contributing to tumor growth and 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, branching and patrolling activity of myeloid cells is increased, and their phagocytic activity is promoted. Modulation of gene expression depends on interferon-(IFN) g produced by natural killer (NK) cells, disappearing in mice depleted of NK cells or lacking IFN-g, and was mimicked by exogenous interleukin-15 (IL-15). Further, we describe a key role for BDNF 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.

Environmental stimuli shape microglial plasticity in glioma / Garofalo, Stefano; Porzia, Alessandra; Mainiero, Fabrizio; DI ANGELANTONIO, Silvia; Barbara, Cortese; Basilico, Bernadette; Pagani, Francesca; Giorgio, Cignitti; Chece, Giuseppina; Maggio, Roberta; Eve, Tremblay; Julie, Savage; Kanchan, Bisht; Esposito, Vincenzo; Bernardini, Giovanni; Thomas, Seyfried; Jakub, Mieczkowski; Karolina, Stepniak; Bozena, Kaminska; Santoni, Angela; Limatola, Cristina. - In: ELIFE. - ISSN 2050-084X. - ELETTRONICO. - dec. 2017(2017). [10.7554/eLife.33415]

Environmental stimuli shape microglial plasticity in glioma

Stefano Garofalo
Conceptualization
;
Alessandra Porzia
Methodology
;
Fabrizio Mainiero
Supervision
;
Silvia Di Angelantonio
Conceptualization
;
BASILICO, BERNADETTE
Methodology
;
Francesca Pagani
Methodology
;
Giuseppina Chece
Methodology
;
Roberta Maggio
Methodology
;
Vincenzo Esposito
Resources
;
Giovanni Bernardini
Conceptualization
;
Angela Santoni
Conceptualization
;
Cristina Limatola
Writing – Review & Editing
2017

Abstract

In glioma, microglia and infiltrating macrophages are exposed to factors that force them to produce cytokines and chemokines, contributing to tumor growth and 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, branching and patrolling activity of myeloid cells is increased, and their phagocytic activity is promoted. Modulation of gene expression depends on interferon-(IFN) g produced by natural killer (NK) cells, disappearing in mice depleted of NK cells or lacking IFN-g, and was mimicked by exogenous interleukin-15 (IL-15). Further, we describe a key role for BDNF 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.
2017
microglia; NK cells; brain tumour; environment
01 Pubblicazione su rivista::01a Articolo in rivista
Environmental stimuli shape microglial plasticity in glioma / Garofalo, Stefano; Porzia, Alessandra; Mainiero, Fabrizio; DI ANGELANTONIO, Silvia; Barbara, Cortese; Basilico, Bernadette; Pagani, Francesca; Giorgio, Cignitti; Chece, Giuseppina; Maggio, Roberta; Eve, Tremblay; Julie, Savage; Kanchan, Bisht; Esposito, Vincenzo; Bernardini, Giovanni; Thomas, Seyfried; Jakub, Mieczkowski; Karolina, Stepniak; Bozena, Kaminska; Santoni, Angela; Limatola, Cristina. - In: ELIFE. - ISSN 2050-084X. - ELETTRONICO. - dec. 2017(2017). [10.7554/eLife.33415]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1044585
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