Copolymer-1 induces adaptive immune anti-inflammatory glial and neuroprotective responses in a murine model of HIV-1 encephalitis
| Autor: | Lynette M. Smith, Santhi Gorantla, Hannah Sneller, Tsuneya Ikezu, Jianou Liu, Larisa Y. Poluektova, David J. Volsky, Howard E. Gendelman, Adelina Holguin, Huanyu Dou |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Neutrophils T-Lymphocytes Immunology Adaptation Biological HIV Infections Biology Microgliosis Neuroprotection Proinflammatory cytokine Mice Immune system Neurotrophic factors medicine Immunology and Allergy Animals Neuroinflammation Microglia Glatiramer Acetate medicine.disease Astrogliosis Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Neuroprotective Agents Encephalitis Peptides Neuroglia |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0022-1767 |
| Popis: | Copolymer-1 (COP-1) elicits neuroprotective activities in a wide range of neurodegenerative disorders. This occurs, in part, by adaptive immune-mediated suppression of microglial inflammatory responses. Because HIV infection and immune activation of perivascular macrophages and microglia drive a metabolic encephalopathy, we reasoned that COP-1 could be developed as an adjunctive therapy for disease. To test this, we developed a novel animal model system that reflects HIV-1 encephalitis in rodents with both innate and adaptive arms of the immune system. Bone marrow-derived macrophages were infected with HIV-1/vesicular stomatitis-pseudotyped virus and stereotactically injected into the basal ganglia of syngeneic mice. HIV-1 pseudotyped with vesicular stomatitis virus envelope-infected bone marrow-derived macrophages induced significant neuroinflammation, including astrogliosis and microglial activation with subsequent neuronal damage. Importantly, COP-1 immunization reduced astro- and microgliosis while diminishing neurodegeneration. Hippocampal neurogenesis was, in part, restored. This paralleled reductions in proinflammatory cytokines, including TNF-α and IL-1β, and inducible NO synthase, and increases in brain-derived neurotrophic factor. Ingress of Foxp3- and IL-4-expressing lymphocytes into brains of COP-1-immunized animals was observed. We conclude that COP-1 may warrant therapeutic consideration for HIV-1-associated cognitive impairments. |
| Databáze: | OpenAIRE |
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