TY - JOUR
T1 - Phenotypic changes in the brain of SIV-infected macaques exposed to methamphetamine parallel macrophage activation patterns induced by the common gamma-chain cytokine system
AU - Bortell, Nikki
AU - Morsey, Brenda
AU - Basova, Liana
AU - Fox, Howard S.
AU - Marcondes, Maria Cecilia Garibaldi
N1 - Publisher Copyright:
© 2015 Bortell, Morsey, Basova, Fox and Marcondes.
PY - 2015
Y1 - 2015
N2 - One factor in the development of neuroAIDS is the increase in the migration of pro-inflammatory CD8 T cells across the blood-brain barrier. Typically these cells are involved with keeping the viral load down. However, the persistence of above average numbers of CD8 T cells in the brain, not necessarily specific to viral peptides, is facilitated by the upregulation of IL15 from astrocytes, in the absence of IL2, in the brain environment. Both IL15 and IL2 are common gamma chain (γc) cytokines. Here, using the non-human primate model of neuroAIDS, we have demonstrated that exposure to methamphetamine, a powerful illicit drug that has been associated with HIV exposure and neuroAIDS severity, can cause an increase in molecules of the γc system. Among these molecules, IL15, which is upregulated in astrocytes by methamphetamine, and that induces the proliferation of T cells, may also be involved in driving an inflammatory phenotype in innate immune cells of the brain. Therefore, methamphetamine and IL15 may be critical in the development and aggravation of central nervous system immune-mediated inflammatory pathology in HIV-infected drug abusers.
AB - One factor in the development of neuroAIDS is the increase in the migration of pro-inflammatory CD8 T cells across the blood-brain barrier. Typically these cells are involved with keeping the viral load down. However, the persistence of above average numbers of CD8 T cells in the brain, not necessarily specific to viral peptides, is facilitated by the upregulation of IL15 from astrocytes, in the absence of IL2, in the brain environment. Both IL15 and IL2 are common gamma chain (γc) cytokines. Here, using the non-human primate model of neuroAIDS, we have demonstrated that exposure to methamphetamine, a powerful illicit drug that has been associated with HIV exposure and neuroAIDS severity, can cause an increase in molecules of the γc system. Among these molecules, IL15, which is upregulated in astrocytes by methamphetamine, and that induces the proliferation of T cells, may also be involved in driving an inflammatory phenotype in innate immune cells of the brain. Therefore, methamphetamine and IL15 may be critical in the development and aggravation of central nervous system immune-mediated inflammatory pathology in HIV-infected drug abusers.
KW - Gamma-chain cytokines
KW - HIV infections
KW - IL15
KW - Macrophages
KW - Methamphetamine
KW - Microglia
KW - NeuroAIDS
KW - SIV
UR - http://www.scopus.com/inward/record.url?scp=84946736701&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946736701&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2015.00900
DO - 10.3389/fmicb.2015.00900
M3 - Article
C2 - 26441851
AN - SCOPUS:84946736701
SN - 1664-302X
VL - 6
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
IS - SEP
M1 - 00900
ER -