Choroid plexus macrophages proliferate and release toxic factors in response to feline immunodeficiency virus
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Recent observations have suggested that lentiviruses stimulate the proliferation and activation of microglia. A similar effect within the dense macrophage population of the choroid plexus could have significant implications for trafficking of virus and inflammatory cells into the brain. To explore this possibility, we cultured fetal feline macrophages and examined their response to feline immunodeficiency virus (FIV) or the T-cell-derived protein, recombinant human CD40-ligand trimer (rhuCD40-L). The rhCD40-L was the most potent stimulus for macrophage proliferation, often inducing a dramatic increase in macrophage density. Exposure to FIV resulted in a small increase in the number of macrophages and macrophage nuclei labeled with bromodeoxyuridine. The increase in macrophage density after FIV infection also correlated with an increase in neurotoxic activity of the macrophage-conditione d medium. Starting at 16–18 weeks postinfection, well after the peak of viremia, a similar toxic activity was detected in cerebrospinal fluid (CSF) from FIV-infected cats. Toxicity in the CSF increased over time and was paralleled by strong CD18 staining of macrophages/microglia in the choroid plexus and adjacent parenchyma. These results suggest that lentiviral infection of the choroid plexus can induce a toxic inflammatory response that is fueled by local macrophage proliferation. Together with the observation of increasing toxic activity in the CSF and increased CD18 staining in vivo, these observations suggest that choroid plexus macrophages may contribute to an inflammatory cascade in the brain that progresses independently of systemic and CSF viral load.
Keywordshuman immunodeficiency virus brain AIDS neural culture neurotoxicity
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- Bragg DC, Robertson K, Hall CD, Meeker RB (2000). Techniques to measure neurologic disease progression in HIV-1 patients. Science Online: NeuroAIDS 3: 1–9.Google Scholar
- Dean AF, Montgomery M, Baskerville A, Cook RW, Cranage MP, Sharpe SA, Dennis MJ, Luthert PJ, Hou S-T, Lantos PL (1993). Different patterns of neuropathological disease in rhesus monkeys infected by simian immunodeficiency virus, and their relation to the humoral immune response. Neuropathol Appl Neurobiol 19: 336–345.PubMedCrossRefGoogle Scholar
- Gelbard HA, Nottet HS, Swindells S, Jett M, Dzenko KA, Genis P, White R, Wang L, Choi Y-B, Zhang D, Lipton SA, Tourtellotte WW, Epstein LG, Gendelman HE (1994). Platelet-activating factor: a candidate human immunodeficiency virus type 1-induced neurotoxin. J Virol 68: 4628–4635.PubMedCentralPubMedGoogle Scholar
- Meeker RB, English R, Tompkins M (1996). Enhanced excitotoxicity in primary feline neural cultures exposed to feline immunodeficiency virus (FIV). J NeuroAIDS 1: 1–27.Google Scholar
- Poli A, Pistello M, Carli MA, Abramo F, Mancuso G, Nicoletti E, Bendinelli M (1999). Tumor necrosis factor-alpha and virus expression in the central nervous system of cats infected with feline immunodeficiency virus. J Neuro Virol 5: 465–473.Google Scholar
- Sopper S, Demuth M, Stahl-Hennig C, Hunsmann G, Plesker R, Coulibaly C, Czub S, Ceska M, Koutsilieri E, Riederer P, Brinkmann R, Katz M, ter Meulen V (1996). The effect of simian immunodeficiency virus infection in vitro and in vivo on the cytokine production of isolated microglia and peripheral macrophages from rhesus monkey. Virology 220: 320–329.PubMedCrossRefGoogle Scholar
- Wesselingh SL, Takahashi K, Glass JD, McArthur JC, Griffin JW, Griffin DE (1997). Cellular localization of tumor necrosis factor mRNA in neurological tissue from HIV-infected patients by combined reverse transcriptase/polymerase chain reaction in situ hybridization and immunohistochemistry. J Neuroimmunol 74: 1–8.PubMedCrossRefGoogle Scholar
- Xiong H, Zeng YC, Lewis T, Zheng J, Persidsky Y, Gendelman HE (2000). HIV-1 infected mononuclear phagocyte secretory products affect neuronal physiology leading to cellular demise: relevance for HIV-1-associated dementia. J Neuro Virol 6(Suppl 1): S14-S23.Google Scholar