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.
Article and author information
Author details
Silvia Di Angelantonio
Funding
Associazione Italiana per la Ricerca sul Cancro (AIRC2015 IG16699)
- Cristina Limatola
Ministero Istruzione Università Ricerca (PRIN 2015)
- Cristina Limatola
CRCHU (Starting Grant)
- Eve Tremblay
European Commission (Euronanomed2: Nanoglio)
- Angela Santoni
Associazione Italiana per la Ricerca sul Cancro (AIRC2014 IG16014)
- Angela Santoni
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The protocol was approved by the Ministry of Health of Italy in accordance with the guidelines on the ethical use of animals from the EC council directive of September 22, 2010 (2010/63/EU).
Reviewing Editor
- Serge Przedborski, Columbia University Medical Center, United States
Publication history
- Received: November 9, 2017
- Accepted: December 28, 2017
- Accepted Manuscript published: December 29, 2017 (version 1)
- Version of Record published: January 19, 2018 (version 2)
Copyright
© 2017, Garofalo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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