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Elife. 2017 Dec 29;6. pii: e33415. doi: 10.7554/eLife.33415.

Environmental stimuli shape microglial plasticity in glioma.

Author information

1
IRCCS Neuromed, Pozzilli, Italy.
2
Department of Experimental Medicine, Sapienza University, Rome, Italy.
3
Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.
4
Center for Life Nanoscience, Istituto Italiano di Tecnologia, Rome, Italy.
5
Consiglio Nazionale delle Ricerche, Institute of Nanotechnology, Rome, Italy.
6
Département de médecine moléculaire, Université Laval, Quebec, Canada.
7
Department of Neurology and Psychiatry, Sapienza University, Rome, Italy.
8
Department of Molecular Medicine, Sapienza University, Rome, Italy.
9
Biology Department, Boston College, boston, United States.
10
Neurobiology Center, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland.
11
Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.

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.

KEYWORDS:

Glioma; NK cells; enriched environment; microglia; mouse; mouse model; neuroscience

PMID:
29286001
PMCID:
PMC5774898
DOI:
10.7554/eLife.33415
[Indexed for MEDLINE]
Free PMC Article

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