Environmental stimuli shape microglial plasticity in glioma

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournaleLife
Volume6
DOIs
Publication statusPublished - Dec 29 2017

Keywords

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

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    Garofalo, S., Porzia, A., Mainiero, F., Di Angelantonio, S., Cortese, B., Basilico, B., Pagani, F., Cignitti, G., Chece, G., Maggio, R., Tremblay, M-E., Savage, J., Bisht, K., Esposito, V., Bernardini, G., Seyfried, T., Mieczkowski, J., Stepniak, K., Kaminska, B., ... Limatola, C. (2017). Environmental stimuli shape microglial plasticity in glioma. eLife, 6. https://doi.org/10.7554/eLife.33415