TY - JOUR
T1 - Proteomic modeling for HIV-1 infected microglia-astrocyte crosstalk
AU - Wang, Tong
AU - Gong, Nan
AU - Liu, Jianuo
AU - Kadiu, Irena
AU - Kraft-Terry, Stephanie D.
AU - Mosley, R. Lee
AU - Volsky, David J.
AU - Ciborowski, Pawel
AU - Gendelman, Howard E.
N1 - Funding Information:
We thank Joshua D Schlautman and Jayme Horning for their great support for LC/MS/MS and MALDI-TOF protein identification. Also we thank James Talaska and Janice Taylor of the Confocal Laser Scanning Microscope Core Facility, University of Nebraska Medical Center, which is supported by the Nebraska Research Initiative, for providing assistance with confocal microscopy. We also acknowledge Dr. Tsuneya Ikezu and Mr. Michael T. Jacobsen of Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, for their professional support for the live imaging assay. The authors wish to thank Dr. Shengyuan Ding for assistance in performance of the migratory assays and immunohistochemical tests.
PY - 2008/6/25
Y1 - 2008/6/25
N2 - Background: HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia) secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system's microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease. Methods and Findings: MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species. Conclusions: These observations provide unique insights into glial crosstalk during disease by supporting astrocyte-mediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery and therapeutics that may influence the course of HIV-1-mediated neurodegeneration.
AB - Background: HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia) secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system's microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease. Methods and Findings: MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species. Conclusions: These observations provide unique insights into glial crosstalk during disease by supporting astrocyte-mediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery and therapeutics that may influence the course of HIV-1-mediated neurodegeneration.
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U2 - 10.1371/journal.pone.0002507
DO - 10.1371/journal.pone.0002507
M3 - Article
C2 - 18575609
AN - SCOPUS:49249136256
SN - 1932-6203
VL - 3
JO - PloS one
JF - PloS one
IS - 6
M1 - e2507
ER -