Environmental stimuli shape microglial plasticity in glioma
- IRCCS Neuromed, Italy
- Sapienza University, Italy
- Consiglio Nazionale delle Ricerche, Italy
- Istituto Italiano di Tecnologia, Italy
- Université Laval, Canada
- Boston College, United States
- Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Poland
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.
Reviewing Editor
- Serge Przedborski, Columbia University Medical Center, United States
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).
Version 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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Environmental stimuli shape microglial plasticity in glioma
eLife 6:e33415.
https://doi.org/10.7554/eLife.33415
Further reading
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- Neuroscience
Probing memory of a complex visual image within a few hundred milliseconds after its disappearance reveals significantly greater fidelity of recall than if the probe is delayed by as little as a second. Classically interpreted, the former taps into a detailed but rapidly decaying visual sensory or ‘iconic’ memory (IM), while the latter relies on capacity-limited but comparatively stable visual working memory (VWM). While iconic decay and VWM capacity have been extensively studied independently, currently no single framework quantitatively accounts for the dynamics of memory fidelity over these time scales. Here, we extend a stationary neural population model of VWM with a temporal dimension, incorporating rapid sensory-driven accumulation of activity encoding each visual feature in memory, and a slower accumulation of internal error that causes memorized features to randomly drift over time. Instead of facilitating read-out from an independent sensory store, an early cue benefits recall by lifting the effective limit on VWM signal strength imposed when multiple items compete for representation, allowing memory for the cued item to be supplemented with information from the decaying sensory trace. Empirical measurements of human recall dynamics validate these predictions while excluding alternative model architectures. A key conclusion is that differences in capacity classically thought to distinguish IM and VWM are in fact contingent upon a single resource-limited WM store.
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- Neuroscience
Our ability to recall details from a remembered image depends on a single mechanism that is engaged from the very moment the image disappears from view.
