Neuroinflammatory responses from microglia recovered from HIV-1-infected and seronegative subjects.

Microglial and macrophage infection and immune activation underlie the pathogenesis of HIV-1-associated dementia (HAD). To assess microglial function in HAD, we isolated cells from brain tissues recovered from an HIV-1-infected patient within 4 h of death. Brain tissue from seronegative patients served as controls. Regional neuropathology was correlated to microglial function. HIV-1-patient microglia formed multinucleated giant cells and produced progeny virions. These microglia secreted reduced basal and LPS-stimulated TNF-alpha levels compared to controls. Monocytes from seronegative donors paralleled these diminished immune responses following repeated LPS-activation. These results demonstrate changes in innate microglial function following viral infection or chronic immune activation.