Microglial clearance function in health and disease

Napoli, Isabella; Neumann, Harald

doi:10.1016/j.neuroscience.2008.06.046

Cited by 270 publications

(229 citation statements)

References 67 publications

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“…However, investigators have reported that in the event of spinal cord injury and ischemic stroke, these cells act as the surveillance system to combat inflammatory cells, secrete various neurotropic factors and anti-inflammatory cytokines (e.g. TGF␤, IL-10), remove cellular debris and oxidized molecules generated from the CNS damage, enhance cell proliferation and differentiation, and eventually maintain the homeostasis of the neural environment (42)(43)(44)(45)(46)(47). The mechanisms that dictate the functional outcomes that are related to either destructive neurodegenerative phenotypes or neuroprotective tissue repair phenotypes need to be clarified, especially with regard to the role of glial cell activation.…”

Section: Discussionmentioning

confidence: 99%

Developmental Onset of Bilirubin-induced Neurotoxicity Involves Toll-like Receptor 2-dependent Signaling in Humanized UDP-glucuronosyltransferase1 Mice

Yueh

Chen

Nguyen

et al. 2014

Journal of Biological Chemistry

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Background: Neonatal jaundice with dangerously high levels of serum bilirubin leads to neurological toxicity. Results: Toll-like receptor 2 signaling is essential for regulation of glia activation, neuroinflammation, and oxidative stress when neonatal mice experience severe hyperbilirubinemia. Conclusion: Toll-like receptor 2 signaling is linked to a protection mode against serum bilirubin-induced brain toxicity. Significance: Understanding how signaling from innate immunity contributes to bilirubin-induced pathology.

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Section: Discussionmentioning

confidence: 99%

Developmental Onset of Bilirubin-induced Neurotoxicity Involves Toll-like Receptor 2-dependent Signaling in Humanized UDP-glucuronosyltransferase1 Mice

Yueh

Chen

Nguyen

et al. 2014

Journal of Biological Chemistry

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“…Induction of select innate immune mechanisms represent the hallmark of several neurodegenerative diseases, which are agedependent, sex-dependent, and host genetic background-dependent and are frequently apparent as a fine balance between beneficial and adverse effects, depending on the immune molecules implicated (45,46). In fact, limited neuroinflammation was evident in the FIV model at week 6 postinfection (Supplemental Fig.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Lentivirus Neurovirulence by Lipopolysaccharide Conditioning: Suppression of CXCL10 in the Brain by IL-10

Maingat

Viappiani

Zhu

et al. 2009

The Journal of Immunology

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Lentivirus infections including HIV and feline immunodeficiency virus (FIV) cause neurovirulence, which is largely mediated by innate immunity. To investigate the interactions between neurovirulence and repeated conditioning by innate immune activation, models of lentivirus infection were exposed to LPS. Gene expression in HIV-infected (HIV+) and control (HIV−) patient brains was compared by real time RT-PCR and immunocytochemistry. Supernatants from mock and HIV-infected monocyte-derived macrophages exposed to LPS were applied to human neurons. FIV-infected (FIV+) and control (FIV−) animals were exposed repeatedly to LPS postinfection together with concurrent neurobehavioral testing, viral load, and host gene analyses. Brains from HIV+ individuals exhibited induction of CD3ε, CXCL10, and granzyme A expression (p < 0.05). Supernatants from HIV+ monocyte-derived macrophages induced CXCL10 expression in neurons, which was diminished by IL-10 treatment (p < 0.05). LPS-exposed FIV+ animals demonstrated lower plasma and brain viral loads (p < 0.05). Neuronal CXCL10 expression was increased in FIV+ animals but was suppressed by LPS exposure, together with reduced brain CD3ε and granzyme A expression (p < 0.05). In conjunction with preserved NeuN-positive neuronal counts in parietal cortex (p < 0.05), FIV+ animals exposed to LPS also showed less severe neurobehavioral deficits (p < 0.05). Repeated LPS exposures suppressed CXCL10 in the brain and ensuing T cell infiltration with a concomitant reduction in neurovirulence. Thus, innate immune chronic conditioning exerted beneficial effects on neurovirulence through suppression of a specific chemotactic factor, CXCL10, mediated by IL-10, leading to reduced leukocyte infiltration and release of neurotoxic factors.

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“…Microglia express many phagocytic surface receptors, including complement receptors [36][37][38]. In the innate immune system, invading pathogens and debris are eliminated by complement.…”

Section: Synaptic Pruning and Neuronal Developmentmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

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Neuroinflammation is the response of the central nervous system (CNS) to disturbed homeostasis and typifies all neurological diseases. The main reactive components of the CNS include microglial cells and infiltrating myeloid cells, astrocytes, oligodendrocytes, and the blood-brain b a r r i e r , c y t o k i n e s , a n d c y t o k i n e s i g n a l i n g . Neuroinflammatory responses may be helpful or harmful, as mechanisms associated with neuroinflammation are involved in normal brain development, as well as in neuropathological processes. This review examines the roles of various cell types that contribute to the immune dysregulation associated with neuroinflammation. Microglia enter the CNS very early in embryonic development and, as such, play an essential role in both the healthy and diseased brain. B-cell diversity contributes to CNS disease through both antibody-dependent and antibody-independent mechanisms. The influences of these B-cell mechanisms on other cell types, including myeloid cells and T cells, are reviewed in relationship to antibody-mediated CNS disorders, paraneoplastic neurological diseases, and multiple sclerosis. New insights into neuroinflammation offer exciting opportunities to investigate potential therapeutic targets for debilitating CNS diseases.

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Microglial clearance function in health and disease

Cited by 270 publications

References 67 publications

Developmental Onset of Bilirubin-induced Neurotoxicity Involves Toll-like Receptor 2-dependent Signaling in Humanized UDP-glucuronosyltransferase1 Mice

Developmental Onset of Bilirubin-induced Neurotoxicity Involves Toll-like Receptor 2-dependent Signaling in Humanized UDP-glucuronosyltransferase1 Mice

Regulation of Lentivirus Neurovirulence by Lipopolysaccharide Conditioning: Suppression of CXCL10 in the Brain by IL-10

Neuroinflammation: Ways in Which the Immune System Affects the Brain

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