Neuroregulatory events follow adaptive immune-mediated elimination of HIV-1-infected macrophages: Studies in a murine model of viral encephalitis

Larisa Y Poluektova, Santhi Gorantla, Jill Faraci, Kevin Birusingh, Huanyu Dou, Howard Eliot Gendelman

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Abstract

HIV-1-specific cellular immunity serves to eliminate infected cells and disease. However, how this process specifically affects the CNS is poorly understood. To mirror the regulatory events that occur in human brain after HIV-1 infection, a murine model of viral encephalitis was used to study relationships, over time, among lymphocyte-mediated infected cell elimination, innate immune responses, and neuropathology. Nonobese diabetic SCID mice were reconstituted with human PBL and a focal encephalitis induced by intracranial injection of autologous HIV-1-infected, monocyte-derived macrophages (MDM). On days 7, 14, and 21 after MDM injection into the basal ganglia, the numbers of human lymphocytes and mouse monocytes, virus-infected MDM, glial (astrocyte and microglial) responses, cytokines, inducible NO (iNOS), neurotrophic factors, and neuronal Ags were determined in brain by immunohistochemistry, real-time PCR, and Western blot assays. Microglia activation, astrocytosis, proinflammatory cytokines, and iNOS expression accompanied the loss of neuronal Ags. This followed entry of human lymphocytes and mouse monocytes into the brain on days 7 and 14. Elimination of virus-infected human MDM, expression of IL-10, neurotropins, and a down-regulation of iNOS coincided with brain tissue restoration. Our results demonstrate that the degree of tissue damage and repair parallels the presence of infected macrophages and effectors of innate and adaptive immunity. This murine model of HIV-1 encephalitis can be useful in elucidating the role played by innate and adaptive immunity in disease progression and resolution.

Original languageEnglish (US)
Pages (from-to)7610-7617
Number of pages8
JournalJournal of Immunology
Volume172
Issue number12
DOIs
StatePublished - Jun 15 2004

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Viral Encephalitis
HIV-1
Macrophages
Innate Immunity
Brain
Adaptive Immunity
Encephalitis
Monocytes
Lymphocytes
Cytokines
Viruses
Inbred NOD Mouse
Injections
Gliosis
SCID Mice
Nerve Growth Factors
Lymphocyte Count
Microglia
Basal Ganglia
Cellular Immunity

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Neuroregulatory events follow adaptive immune-mediated elimination of HIV-1-infected macrophages: Studies in a murine model of viral encephalitis",
abstract = "HIV-1-specific cellular immunity serves to eliminate infected cells and disease. However, how this process specifically affects the CNS is poorly understood. To mirror the regulatory events that occur in human brain after HIV-1 infection, a murine model of viral encephalitis was used to study relationships, over time, among lymphocyte-mediated infected cell elimination, innate immune responses, and neuropathology. Nonobese diabetic SCID mice were reconstituted with human PBL and a focal encephalitis induced by intracranial injection of autologous HIV-1-infected, monocyte-derived macrophages (MDM). On days 7, 14, and 21 after MDM injection into the basal ganglia, the numbers of human lymphocytes and mouse monocytes, virus-infected MDM, glial (astrocyte and microglial) responses, cytokines, inducible NO (iNOS), neurotrophic factors, and neuronal Ags were determined in brain by immunohistochemistry, real-time PCR, and Western blot assays. Microglia activation, astrocytosis, proinflammatory cytokines, and iNOS expression accompanied the loss of neuronal Ags. This followed entry of human lymphocytes and mouse monocytes into the brain on days 7 and 14. Elimination of virus-infected human MDM, expression of IL-10, neurotropins, and a down-regulation of iNOS coincided with brain tissue restoration. Our results demonstrate that the degree of tissue damage and repair parallels the presence of infected macrophages and effectors of innate and adaptive immunity. This murine model of HIV-1 encephalitis can be useful in elucidating the role played by innate and adaptive immunity in disease progression and resolution.",
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AU - Poluektova, Larisa Y

AU - Gorantla, Santhi

AU - Faraci, Jill

AU - Birusingh, Kevin

AU - Dou, Huanyu

AU - Gendelman, Howard Eliot

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