Assessing Microglial Dynamics by Live Imaging

Andoh, Megumi; Koyama, Ryuta

doi:10.3389/fimmu.2021.617564

Cited by 14 publications

(11 citation statements)

References 110 publications

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“…This assumption was motivated by the data on microglial motility in extending its processes to injury within hours (Davalos et al, 2005) and showing morphological changes (e.g. enlarged soma and shortening of processes) already 48 hours after the status epilepticus (Andoh and Koyama, 2021). The other described processes (vasculature recovery, neuronal loss and debris removal, circuit remodeling) take longer time.…”

Section: Model Parameter Choicementioning

confidence: 99%

A mathematical model of neuroimmune interactions in epileptogenesis for discovering treatment strategies

et al. 2022

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Section: Model Parameter Choicementioning

confidence: 99%

A mathematical model of neuroimmune interactions in epileptogenesis for discovering treatment strategies

et al. 2022

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“…This result is in agreement with findings that M1-like microglia, showing augmented release of NO and expression of pro-inflammatory cytokines, more efficiently phagocytose pathogenic bacteria than unstimulated microglia, but M2-like microglia were not examined ( 51 , 52 ). Studies comparing in vitro phagocytosis dynamics between different microglia subtypes over time are scarce ( 53 ). Therefore, we conducted live imaging experiments over 16 hours in anticipation of gaining new insights.…”

Section: Discussionmentioning

confidence: 99%

Microglia subtypes show substrate- and time-dependent phagocytosis preferences and phenotype plasticity

Wernersbach

Harms

et al. 2022

Front. Immunol.

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Microglia are phagocytosis-competent CNS cells comprising a spectrum of subtypes with beneficial and/or detrimental functions in acute and chronic neurodegenerative disorders. The heterogeneity of microglia suggests differences in phagocytic activity and phenotype plasticity between microglia subtypes. To study these issues, primary murine glial cultures were cultivated in the presence of serum, different growth factors and cytokines to obtain M0-like, M1-like, and M2-like microglia as confirmed by morphology, M1/M2 gene marker expression, and nitric oxide assay. Single-cell analysis after 3 hours of phagocytosis of E.coli particles or IgG-opsonized beads showed equal internalization by M0-like microglia, whereas M1-like microglia preferably internalized E.coli particles and M2-like microglia preferably internalized IgG beads, suggesting subtype-specific preferences for different phagocytosis substrates. Time-lapse live-cells imaging over 16 hours revealed further differences between microglia subtypes in phagocytosis preference and internalization dynamics. M0- and, more efficiently, M1-like microglia continuously internalized E.coli particles for 16 hours, whereas M2-like microglia discontinued internalization after approximately 8 hours. IgG beads were continuously internalized by M0- and M1-like microglia but strikingly less by M2-like microglia. M2-like microglia initially showed continuous internalization similar to M0-like microglia but again discontinuation of internalization after 8 hours suggesting that the time of substrate exposure differently affect microglia subtypes. After prolonged exposure to E.coli particles or IgG beads for 5 days all microglia subtypes showed increased internalization of E.coli particles compared to IgG beads, increased nitric oxide release and up-regulation of M1 gene markers, irrespectively of the phagocytosis substrate, suggesting phenotype plasticity. In summary, microglia subtypes show substrate- and time-dependent phagocytosis preferences and phenotype plasticity. The results suggest that prolonged phagocytosis substrate exposure enhances M1-like profiles and M2-M1 repolarization of microglia. Similar processes may also take place in conditions of acute and chronic brain insults when microglia encounter different types of phagocytic substrates.

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“…It is possible that phagocytes depend on the energy produced by the degradation reaction for their survival. In particular, these cells move their cytoskeletons dynamically, for example, during migration and in the formation of phagocytic cups [116], and they are expected to consume a large amount of energy compared to nonphagocytic cells. Phagocytes may phagocytose to obtain energy for further phagocytosis.…”

Section: Acquisition Of Nutrientsmentioning

confidence: 99%

Comparative Review of Microglia and Monocytes in CNS Phagocytosis

Andoh

Koyama

2021

Cells

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Macrophages maintain tissue homeostasis by phagocytosing and removing unwanted materials such as dead cells and cell debris. Microglia, the resident macrophages of the central nervous system (CNS), are no exception. In addition, a series of recent studies have shown that microglia phagocytose the neuronal synapses that form the basis of neural circuit function. This discovery has spurred many neuroscientists to study microglia. Importantly, in the CNS parenchyma, not only microglia but also blood-derived monocytes, which essentially differentiate into macrophages after infiltration, exert phagocytic ability, making the study of phagocytosis in the CNS even more interesting and complex. In particular, in the diseased brain, the phagocytosis of tissue-damaging substances, such as myelin debris in multiple sclerosis (MS), has been shown to be carried out by both microglia and blood-derived monocytes. However, it remains largely unclear why blood-derived monocytes need to invade the parenchyma, where microglia are already abundant, to assist in phagocytosis. We will also discuss whether this phagocytosis can affect the fate of the phagocytosing cell itself as well as the substance being phagocytosed and the surrounding environment in addition to future research directions. In this review, we will introduce recent studies to answer a question that often arises when studying microglial phagocytosis: under what circumstances and to what extent blood-derived monocytes infiltrate the CNS and contribute to phagocytosis. In addition, the readers will learn how recent studies have experimentally distinguished between microglia and infiltrating monocytes. Finally, we aim to contribute to the progress of phagocytosis research by discussing the effects of phagocytosis on phagocytic cells.

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Assessing Microglial Dynamics by Live Imaging

Cited by 14 publications

References 110 publications

A mathematical model of neuroimmune interactions in epileptogenesis for discovering treatment strategies

A mathematical model of neuroimmune interactions in epileptogenesis for discovering treatment strategies

Microglia subtypes show substrate- and time-dependent phagocytosis preferences and phenotype plasticity

Comparative Review of Microglia and Monocytes in CNS Phagocytosis

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