title: SIV encephalitis lesions are composed of CD163(+) macrophages present in the central nervous system during early SIV infection and SIV-positive macrophages recruited terminally with AIDS.
abstract: Macrophage recruitment to the central nervous system (CNS) during AIDS pathogenesis is poorly understood. We measured the accumulation of brain perivascular (CD163(+)) and inflammatory (MAC387(+)) macrophages in SIV-infected monkeys. Monocyte progenitors were 5-bromo-2'-deoxyuridine (BrdU) labeled in bone marrow, and CNS macrophages were labeled serially with fluorescent dextrans injected into the cisterna magna. MAC387(+) macrophages accumulated in the meninges and choroid plexus in early inflammation and in the perivascular space and SIV encephalitis (SIVE) lesions late. CD163(+) macrophages accumulated in the perivascular space and SIVE lesions with late inflammation. Most of the BrdU(+) cells were MAC387(+); however, CD163(+)BrdU(+) macrophages were present in the meninges and choroid plexus with AIDS. Most (81.6% ± 1.8%) of macrophages in SIVE lesions were present in the CNS before SIVE lesion formation. There was a 2.9-fold increase in SIVp28(+) macrophages entering the CNS late compared with those entering early (P < 0.05). The rate of CD163(+) macrophage recruitment to the CNS inversely correlated with time to death (P < 0.03) and increased with SIVE. In SIVE animals, soluble CD163 correlated with CD163(+) macrophage recruitment (P = 0.02). Most perivascular macrophages that comprise SIVE lesions and multinucleated giant cells are present in the CNS early, before SIVE lesions are formed. Most SIV-infected macrophages traffic to the CNS terminally with AIDS.
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Nowlin
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Tricia H
authors.initials: TH
authors.lastname: Burdo
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Tulane University Health Science Center, Covington, Louisiana.
authors.forename: Cecily C
authors.initials: CC
authors.lastname: Midkiff
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, Emerging Pathogens Institute, University of Florida, Gainesville, Florida.
authors.forename: Marco
authors.initials: M
authors.lastname: Salemi
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Tulane University Health Science Center, Covington, Louisiana.
authors.forename: Xavier
authors.initials: X
authors.lastname: Alvarez
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Massachusetts. Electronic address: kenneth.williams.3@bc.edu.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Williams
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D004660:Encephalitis / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta; D008264:Macrophages / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus