CD163 Identifies Perivascular Macrophages in Normal and Viral Encephalitic Brains and Potential Precursors to Perivascular Macrophages in Blood

Kim, Woong‐Ki; Álvarez, Xavier; Fisher, Jeanne Y.; Bronfin, Benjamin; Westmoreland, Susan V.; McLaurin, JoAnne; Williams, Kenneth C.

doi:10.2353/ajpath.2006.050215

Cited by 187 publications

(218 citation statements)

References 78 publications

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“…After intracranial injection, the hydrophilic fluorescent dextran dyes diffuse along the perivascular space and are absorbed by essentially all perivascular macrophages (>98%) via non-specific micropinocytosis. 25,30,49 To establish a baseline for subsequent perivascular macrophage turnover, all animals (n Z 12) received fluoresceinconjugated dextran (abbreviated Dextran:FITC; Molecular Probes) at 20 dpi (Table 1). Five animals received a second injection of Alexa Fluor 647econjugated dextran (abbreviated Dextran:AF647; Molecular Probes) 48 hours before necropsy to determine macrophage recruitment from 20 dpi necropsy.…”

Section: Intracisternal Injection Of Dextran Amines and Detection In mentioning

confidence: 99%

“…9,24,25 Parenchymal microglia, the resident macrophages of the CNS, are yolk sacederived, myeloid lineage cells that engraft the CNS during embryonic development and are then maintained as a stable population. 26,27 Perivascular, meningeal, and choroid plexus macrophages are of bone marrow origin and are thought to be replenished from circulating monocytes in rodents, nonhuman primates, and humans, likely at different rates.…”

mentioning

confidence: 99%

“…17,28e32 In the normal CNS, microglia express the pan-macrophage marker CD68 and have low to undetectable hemoglobin-haptoglobin scavenger receptor CD163 (CD68 þ CD163 À ). 25 Perivascular macrophages express both CD163 and CD68 (CD163 þ CD68 þ ). 25 A third phenotypic population of macrophages is labeled by the antibody MAC387, which recognizes migration inhibitory factorerelated protein (MRP) 14 or the MRP8/MRP14 heterodimer, but does not have detectable CD68 or CD163 (MAC387 þ CD68 À CD163 À ).…”

mentioning

confidence: 99%

“…25 Perivascular macrophages express both CD163 and CD68 (CD163 þ CD68 þ ). 25 A third phenotypic population of macrophages is labeled by the antibody MAC387, which recognizes migration inhibitory factorerelated protein (MRP) 14 or the MRP8/MRP14 heterodimer, but does not have detectable CD68 or CD163 (MAC387 þ CD68 À CD163 À ). 14 MAC387 þ macrophages are not present in the uninfected or noninflamed CNS but are recruited with inflammation.…”

mentioning

confidence: 99%

“…5,7 MAC387 þ macrophages are rarely found to be productively infected. 9,13,14,25,37 The timing of monocyte and macrophage entry into the CNS and the role of macrophage subsets mediating the progression or resolution of CNS inflammation due to HIV and SIV infection are not well defined.…”

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confidence: 99%

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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

Nowlin

Burdo

Midkiff

et al. 2015

The American Journal of Pathology

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Macrophage recruitment to the central nervous system (CNS) during AIDS pathogenesis is poorly understood. We measured the accumulation of brain perivascular (CD163 þ ) and inflammatory (MAC387 þ ) macrophages in SIV-infected monkeys. Monocyte progenitors were 5-bromo-2 0 -deoxyuridine (BrdU) labeled in bone marrow, and CNS macrophages were labeled serially with fluorescent dextrans injected into the cisterna magna. MAC387 þ macrophages accumulated in the meninges and choroid plexus in early inflammation and in the perivascular space and SIV encephalitis (SIVE) lesions late. CD163 þ macrophages accumulated in the perivascular space and SIVE lesions with late inflammation. Most of the BrdU þ cells were MAC387 þ ; however, CD163 þ BrdU þ macrophages were present in the meninges and choroid plexus with AIDS. Most (81.6% AE 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 þ macrophages entering the CNS late compared with those entering early (P < 0.05). The rate of CD163 þ 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 þ macrophage recruitment (P Z 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.

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Section: Intracisternal Injection Of Dextran Amines and Detection In mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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

Nowlin

Burdo

Midkiff

et al. 2015

The American Journal of Pathology

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The role and therapeutic potential of monocytic cells in Alzheimer's disease

Malm

Koistinaho

Muona

et al. 2010

Glia

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Alzheimer's disease (AD) is a dementing neurodegenerative disorder without a cure. The abnormal parenchymal accumulation of b-amyloid (Ab) is associated with inflammatory reactions involving microglia and astrocytes. Increased levels of Ab and Ab deposition in the brain are thought to cause neuronal dysfunction and underlie dementia. Microglia, the brain resident cells of monocytic origin, have a potential ability to phagocytose Ab but they also react to Ab by increased production of proinflammatory toxic agents. Microglia originate from hemangioblastic mesoderm during early embryonic stages and from bone marrow (BM)-derived monocytic cells that home the brain throughout the neonatal stage of development. Recent studies indicate that BM or blood-derived monocytes are recruited to the diseased AD brain, associate with the Ab depositions, and are more efficient phagocytes of Ab compared with resident microglia. The clearance of Ab deposition by these cells has been recently under intensive investigation and can occur through several different mechanisms. Importantly, peripheral monocytic cells of patients with AD appear to be deficient in clearing Ab. This review will summarize the findings on the role of blood-derived cells in AD and discuss their therapeutic potential for treating patients suffering from this devastating disease. V

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Antiretroviral therapy restores the homeostatic state of microglia in SIV-infected rhesus macaques

Trease

Niu

Morsey

et al. 2022

Journal of Leukocyte Biology

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Microglia and macrophages are essential for homeostatic maintenance and innate immune response in the brain. They are the first line of defense against infections such as HIV/SIV in the brain. However, they are susceptible to infection and function as viral reservoirs even under effective viral suppression. While current antiretroviral regimens successfully suppress viremia and improve quality of life and lifespan, neurologic complications persist and are in part attributed to activated microglia. We sought to test the hypothesis that brain microglia return to a more homeostatic‐like state when viremia is suppressed by combination antiretroviral therapy. Using the SIV‐rhesus macaque model, we combined single‐cell RNA sequencing, bioinformatics, and pathway analysis to compare gene expression profiles of brain myeloid cells under 4 conditions: uninfected, SIV infected, SIV infected with cART suppression, and SIV encephalitis (SIVE). Our study reveals greater myeloid diversity and an elevated proinflammatory state are associated with untreated SIV infection compared with uninfected animals. The development of encephalitis and suppression of viremia both reduced myeloid diversity. However, they had converse effects on the activation state of microglia and inflammation. Notably, suggestive of a restoration of a homeostatic state in microglia, gene expression and activation of pathways related to inflammation and immune response in cART‐suppressed monkeys were most similar to that in uninfected monkeys. Untreated SIV infection shared characteristics, especially in brain macrophages to SIVE, with SIVE showing dramatic inflammation. In support of our hypothesis, our study demonstrates that cART indeed restores this key component of the brain's homeostatic state. Summary: ScRNA‐seq of rhesus monkey microglia reveals clusters of cells in activated states in the setting of SIV infection, which is primarily reversed by suppressing viremia with combination antiretroviral therapy.

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CD163 Identifies Perivascular Macrophages in Normal and Viral Encephalitic Brains and Potential Precursors to Perivascular Macrophages in Blood

Cited by 187 publications

References 78 publications

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

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

The role and therapeutic potential of monocytic cells in Alzheimer's disease

Antiretroviral therapy restores the homeostatic state of microglia in SIV-infected rhesus macaques

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