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BMC Immunology
Published in: BMC Immunology 1/2016

Open Access 01-12-2016 | Research article

Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

Authors: Julia A. Najera, Eduardo A. Bustamante, Nikki Bortell, Brenda Morsey, Howard S. Fox, Timothy Ravasi, Maria Cecilia Garibaldi Marcondes

Published in: BMC Immunology | Issue 1/2016

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Abstract

Background

Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers.

Results

We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load.

Conclusions

Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.
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Metadata
Title
Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets
Authors
Julia A. Najera
Eduardo A. Bustamante
Nikki Bortell
Brenda Morsey
Howard S. Fox
Timothy Ravasi
Maria Cecilia Garibaldi Marcondes
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2016
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-016-0145-0

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