title: Microglia activation by SIV-infected macrophages: alterations in morphology and cytokine secretion.
abstract: HIV infection in the brain and the resultant encephalitis affect approximately one third of individuals infected with HIV, regardless of treatment with antiretroviral drugs. Microglia are the resident phagocytic cell type in the brain, serving as a "first responder" to neuroinvasion by pathogens. The early events of the microglial response to productively infected monocyte/macrophages entering the brain can best be investigated using in vitro techniques. We hypothesized that activation of microglia would be specific to the presence of simian immunodeficiency virus (SIV)-infected macrophages as opposed to responses to macrophages in general. Purified microglia were grown and stimulated with control or SIV-infected macrophages. After 6 h, aliquots of the supernatant were analyzed for 23 cytokines using Millipore nonhuman primate-specific kit. In parallel experiments, morphologic changes and cytokine expression by individual microglia were examined by immunofluorescence. Surprisingly, the presence of macrophages was more important to the microglial response rather than whether the macrophages were infected with SIV. None of the cytokines examined were unique to co-incubation with SIV-infected macrophages compared with control macrophages, or their supernatants. Media from SIV-infected macrophages, however, did induce secretion of higher levels of IL-6 and IL-8 than the other treatments. As resident macrophages in the brain, microglia would be expected to have a strong response to infiltrate innate immune cells such as monocyte/macrophages. This response is triggered by incubation with macrophages, irrespective of whether or not they are infected with SIV, indicating a rapid, generalized immune response when infiltrating macrophages entering the brain.
authors.affiliation: Tulane National Primate Research Center, Tulane University, New Orleans, LA, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Renner
authors.forename: Hope A
authors.initials: HA
authors.lastname: Sansing
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Morici
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Inglis
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
authors.forename: Andrew G
authors.initials: AG
authors.lastname: MacLean
mesh_terms: D000818:Animals; D002450:Cell Communication; D002465:Cell Movement; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D005625:Frontal Lobe / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology* / Q000473:pathology / Q000821:virology; D017628:Microglia / Q000276:immunology* / Q000473:pathology / Q000821:virology; D061251:Primary Cell Culture; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines