Proteomic modeling for HIV-1 infected microglia-astrocyte crosstalk
| Autor: | Stephanie D. Kraft-Terry, Nan Gong, Irena Kadiu, R. Lee Mosley, Pawel Ciborowski, Howard E. Gendelman, Jianuo Liu, David J. Volsky, Tong Wang |
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| Rok vydání: | 2008 |
| Předmět: |
Proteomics
Programmed cell death Immunology lcsh:Medicine Biology 03 medical and health sciences Mice 0302 clinical medicine Immune system Pregnancy Virology medicine Animals Immunology/Cellular Microbiology and Pathogenesis lcsh:Science Cytoskeleton 030304 developmental biology 0303 health sciences Multidisciplinary Microglia Neuroscience/Neuronal and Glial Cell Biology Neurodegeneration lcsh:R Neurotoxicity medicine.disease biology.organism_classification 3. Good health Cell biology Mice Inbred C57BL Crosstalk (biology) medicine.anatomical_structure Vesicular stomatitis virus Astrocytes Virology/Immunodeficiency Viruses Immunology/Immune Response HIV-1 lcsh:Q Female Reactive Oxygen Species Neuroscience/Neurobiology of Disease and Regeneration 030217 neurology & neurosurgery Astrocyte Research Article Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 3, Iss 6, p e2507 (2008) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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