Choroid plexus macrophages proliferate and release toxic factors in response to feline immunodeficiency virus.
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-conditioned 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.
Bragg
D C
DC
Neurobiology Curriculum and Department of Neurology, University of North Carolina, Chapel Hill 27599, USA.
Hudson
L C
LC
Liang
Y H
YH
Tompkins
M B
MB
Fernandes
A
A
Meeker
R B
RB
D000818:Animals; D018821:CD18 Antigens / Q000032:analysis; D023201:CD40 Ligand / Q000494:pharmacology; D002415:Cats; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002831:Choroid Plexus / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003603:Cytotoxins / Q000276:immunology / Q000378:metabolism; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D016089:Immunodeficiency Virus, Feline / Q000276:immunology*; D066298:In Vitro Techniques; D008264:Macrophages / Q000737:chemistry / Q000166:cytology / Q000821:virology*; D009474:Neurons / Q000821:virology; D013047:Specific Pathogen-Free Organisms
D018821:CD18 Antigens; D017077:Culture Media, Conditioned; D003603:Cytotoxins; D023201:CD40 Ligand