title: Monocyte Traffic, Dorsal Root Ganglion Histopathology, and Loss of Intraepidermal Nerve Fiber Density in SIV Peripheral Neuropathy.
abstract: HIV-associated sensory neuropathy remains the most common neurological complication of HIV infection and is characterized by dorsal root ganglion (DRG) inflammation and intraepidermal nerve fiber density (IENFD) loss. Chronic peripheral immune cell activation and accumulation may cause damage to the DRG, but has not been fully investigated yet. By using an SIV-infected, CD8-lymphocyte-depleted rhesus macaque model, we defined immune cells surrounding DRG neurons and their role in DRG pathology, measured cell traffic from the bone marrow to the DRGs using 5-bromo-2-deoxyuridine (BrdU) pulse, and serially measured IENFD. We found an increase in CD68(+) and CD163(+) macrophages in DRGs of SIV-infected animals. MAC387(+) recently recruited monocytes/macrophages were increased, along with BrdU(+) cells, in the DRGs of SIV-infected macaques. We demonstrated that 78.1% of all BrdU(+) cells in DRGs were also MAC387(+). The number of BrdU(+) monocytes correlated with severe DRG histopathology, which included neuronophagia, neuronal loss, and Nageotte nodules. These data demonstrate that newly recruited MAC387(+)BrdU(+) macrophages may play a significant role in DRG pathogenesis. IENFD decreased early (day 21), consistent with the development of sensory neuropathy in SIV-infected macaques. Decreased IENFD was associated with elevated BrdU(+) cells in the DRG. These data suggest that increased recruitment of macrophages to DRG is associated with severe DRG histopathology and IENFD loss.
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Lakritz
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Ayman
authors.initials: A
authors.lastname: Bodair
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Neal
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ryan
authors.initials: R
authors.lastname: O'Donnell
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Polydefkis
authors.affiliation: Department of Biomedical Sciences, Section of Anatomic Pathology, Cornell University College of Veterinary Medicine, Ithaca, New York.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts. Electronic address: burdot@bc.edu.
authors.forename: Tricia H
authors.initials: TH
authors.lastname: Burdo
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000276:immunology / Q000473:pathology*; D015658:HIV Infections / Q000150:complications / Q000473:pathology; D008253:Macaca mulatta; D008264:Macrophages / Q000502:physiology; D009000:Monocytes / Q000502:physiology*; D009412:Nerve Fibers / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000473:pathology* / Q000821:virology; D011897:Random Allocation; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity* / Q000502:physiology; D012867:Skin / Q000294:innervation; D014779:Virus Replication