Distinct macrophage subpopulations regulate viral encephalitis but not viral clearance in the CNS

Steel, Christina; Kim, Woong‐Ki; Sanford, Larry D.; Wellman, Laurie L.; Burnett, Sandra H.; Rooijen, Nico van; Ciavarra, Richard P.

doi:10.1016/j.jneuroim.2010.05.034

Cited by 29 publications

(36 citation statements)

References 46 publications

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“…We and others have successfully targeted rodent PVM to demonstrate the roles of PVM in brain inflammation and infection using liposome-encapsulated clodronate (Polfliet et al 2001, 2002; Audoy-Remus et al 2008; Hawkes and McLaurin 2009; Serrats et al 2010; Steel et al 2010). Bisphosphonates including clodronate and alendronate have been extensively used in small animal models to effectively deplete monocytes and macrophages in vivo when administered in liposomal form (Huitinga et al 1992; Danenberg et al 2003; Sunderkotter et al 2004).…”

Section: Resultsmentioning

confidence: 99%

“…We and others have demonstrated either protective or pathogenic functions of PVM in brain inflammation by depleting rodent PVM using clodronate liposomes (Polfliet et al 2001, 2002; Audoy-Remus et al 2008; Hawkes and McLaurin 2009; Serrats et al 2010; Steel et al 2010). This may reflect functional plasticity or heterogeneity of PVM.…”

Section: Discussionmentioning

confidence: 99%

“…Liposome-encapsulated bisphosphonates including clodronate injected into the lateral cerebral ventricle were able to selectively deplete PVM in mice, rat, and rabbits (Trostdorf et al 1999; Polfliet et al 2001, 2002; Galea et al 2005; Hawkes and McLaurin 2009; Steel et al 2010). We used the same approach to rhesus monkeys to deplete PVM, using a more potent bisphosphonate, alendronate.…”

Section: Methodsmentioning

confidence: 99%

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Expression of the Mannose Receptor CD206 in HIV and SIV Encephalitis: A Phenotypic Switch of Brain Perivascular Macrophages with Virus Infection

Holder

McGary

Johnson

et al. 2014

J Neuroimmune Pharmacol

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We examined the expression of the mannose receptor CD206 by perivascular macrophages (PVM) in normal human and monkey brains and in brains of HIV-infected humans and of monkeys infected with simian immunodeficiency virus (SIV). Depletion of brain PVM in SIV-infected monkeys by intrathecal injection of liposome-encapsulated bisphosphonates eliminated CD206-expressing cells in the brain, confirming their perivascular location and phagocytic capacity. In vivo labeling with bromodeoxyuridine in normal uninfected and SIV-infected macaques in combination with CD206 immunostaining revealed a CD206+-to-CD206– shift within pre-existing PVM during SIV brain infection and neuroinflammation. These findings identify CD206 as a unique marker of human and macaque PVM, and underscore the utility of this marker in studying the origin, turnover and functions of these cells in AIDS.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Expression of the Mannose Receptor CD206 in HIV and SIV Encephalitis: A Phenotypic Switch of Brain Perivascular Macrophages with Virus Infection

Holder

McGary

Johnson

et al. 2014

J Neuroimmune Pharmacol

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“…2) [47]. Similarly, PVM depletion is beneficial in the encephalitis induced by intranasal application of vesicular stomatitis virus (VSV) [48]. Thus, PVM and MGM depletion by CLO suppressed the brain accumulation of neutrophils and T cells, reduced VSV load, and improved motor deficits [48].…”

Section: Pathophysiological Role Of Perivascular Macrophagesmentioning

confidence: 99%

Brain perivascular macrophages: characterization and functional roles in health and disease

et al. 2017

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Perivascular macrophages (PVM) are a distinct population of resident brain macrophages characterized by a close association with the cerebral vasculature. PVM migrate from the yolk sac into the brain early in development and, like microglia, are likely to be a self-renewing cell population that, in the normal state, is not replenished by circulating monocytes. Increasing evidence implicates PVM in several disease processes, ranging from brain infections and immune activation to regulation of the hypothalamic-adrenal axis and neurovascular-neurocognitive dysfunction in the setting of hypertension, Alzheimer disease pathology, or obesity. These effects involve crosstalk between PVM and cerebral endothelial cells, interaction with circulating immune cells, and/or production of reactive oxygen species. Overall, the available evidence supports the idea that PVM are a key component of the brain-resident immune system with broad implications for the pathogenesis of major brain diseases. A better understanding of the biology and pathobiology of PVM may lead to new insights and therapeutic strategies for a wide variety of brain diseases.

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“…or 10 ml/mouse i.c.v., respectively) 72 h prior to IL-4 treatment (42,43). Liposomal clodronate was injected both i.p.…”

Section: Microglia/macrophage Depletionmentioning

confidence: 99%

Phenotypic Polarization of Activated Astrocytes: The Critical Role of Lipocalin-2 in the Classical Inflammatory Activation of Astrocytes

Jang

Kim

Lee

et al. 2013

The Journal of Immunology

189

157

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Astrocytes provide structural and functional support for neurons, as well as display neurotoxic or neuroprotective phenotypes depending upon the presence of an immune or inflammatory microenvironment. This study was undertaken to characterize multiple phenotypes of activated astrocytes and to investigate the regulatory mechanisms involved. We report that activated astrocytes in culture exhibit two functional phenotypes with respect to pro- or anti-inflammatory gene expression, glial fibrillary acidic protein expression, and neurotoxic or neuroprotective activities. The two distinct functional phenotypes of astrocytes were also demonstrated in a mouse neuroinflammation model, which showed pro- or anti-inflammatory gene expression in astrocytes following challenge with classical or alternative activation stimuli; similar results were obtained in the absence of microglia. Subsequent studies involving recombinant lipocalin-2 (LCN2) protein treatment or Lcn2-deficient mice indicated that the pro- or anti-inflammatory functionally polarized phenotypes of astrocytes and their intracellular signaling pathway were critically regulated by LCN2 under in vitro and in vivo conditions. Astrocyte-derived LCN2 promoted classical proinflammatory activation of astrocytes but inhibited IL-4–STAT6 signaling, a canonical pathway involved in alternative anti-inflammatory activation. Our results suggest that the secreted protein LCN2 is an autocrine modulator of the functional polarization of astrocytes in the presence of immune or inflammatory stimuli and that LCN2 could be targeted therapeutically to dampen proinflammatory astrocytic activation and related pathologies in the CNS.

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Distinct macrophage subpopulations regulate viral encephalitis but not viral clearance in the CNS

Cited by 29 publications

References 46 publications

Expression of the Mannose Receptor CD206 in HIV and SIV Encephalitis: A Phenotypic Switch of Brain Perivascular Macrophages with Virus Infection

Expression of the Mannose Receptor CD206 in HIV and SIV Encephalitis: A Phenotypic Switch of Brain Perivascular Macrophages with Virus Infection

Brain perivascular macrophages: characterization and functional roles in health and disease

Phenotypic Polarization of Activated Astrocytes: The Critical Role of Lipocalin-2 in the Classical Inflammatory Activation of Astrocytes

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