Siglec‐h on activated microglia for recognition and engulfment of glioma cells

Kopatz, Jens; Beutner, Clara; Welle, Kristian; Bodea, Liviu‐Gabriel; Reinhardt, Julia; Claude, Janine; Linnartz‐Gerlach, Bettina; Neumann, Harald

doi:10.1002/glia.22501

Cited by 68 publications

(43 citation statements)

References 42 publications

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“…Corroborating this, we found that MZM in spleen (Figure 4A) and medullary macrophages in LN (data not shown) were SiglecH + by immunohistochemistry. In addition, we observed that SiglecH was expressed by CD45 int CD11b + microglia in brain (Figure 4B), in agreement with a recent study (24). …”

Section: Resultssupporting

confidence: 93%

Cell Depletion in Mice That Express Diphtheria Toxin Receptor under the Control of SiglecH Encompasses More Than Plasmacytoid Dendritic Cells

Swiecki

Wang

Riboldi

et al. 2014

The Journal of Immunology

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Plasmacytoid dendritic cells (pDC) produce type I interferon (IFN-I) in response to viruses and are routinely identified in mice by SiglecH expression. SiglecH is a sialic acid-binding immunoglobulin-like lectin that has an immunomodulatory role during viral infections. Here, we evaluated the impact of SiglecH deficiency on cytokine responses in the presence and absence of pDC. We found that lack of SiglecH enhanced IFN-I responses to viral infection regardless of whether pDC were depleted or not. We also examined the expression pattern of SiglecH in this study. We observed that SiglecH was expressed by specialized macrophages and progenitors of classical DC (cDC) and pDC. Accordingly, marginal zone macrophages and pDC precursors were eliminated in newly generated SiglecH-DTR Tg mice but not CLEC4C-DTR Tg mice after diphtheria toxin (DT) treatment. Using two different bacterial models, we found that SiglecH-DTR Tg mice injected with DT had altered bacterial uptake and were more susceptible to lethal Listeria monocytogenes infection than DT-treated CLEC4C-DTR Tg mice. Taken together, our findings suggest that lack of SiglecH may affect cytokine responses by cell types other than pDC during viral infections perhaps by altering viral distribution or burden and that cell depletion in SiglecH-DTR Tg mice encompasses more than pDC.

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Section: Resultssupporting

confidence: 93%

Cell Depletion in Mice That Express Diphtheria Toxin Receptor under the Control of SiglecH Encompasses More Than Plasmacytoid Dendritic Cells

Swiecki

Wang

Riboldi

et al. 2014

The Journal of Immunology

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“…Central to MGM3 lies sialic acid binding Ig-like lectin H ( Siglech). Siglech is a putative marker of isolated microglia (Chiu et al, 2013); which modulates type I Interferon secretion associated with microglial activation and phagocytosis of glioma cells (Blasius et al, 2006; Kopatz et al, 2013). Brain specific expression and function of Siglech has yet to be completely ascertained, however, because MGM3 shows ontologies related to TLR signaling, particularly endosomal TLRs which promote interferon secretion, it is possible that Siglech is regulating this response in brain.…”

Section: Resultsmentioning

confidence: 99%

Microglial-specific transcriptome changes following chronic alcohol consumption

et al. 2018

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Microglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer’s disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis. Coordinate expression of these genes is not ascertained from an admixture of CNS cell-types, underscoring the importance of examining isolated cellular populations to reveal systematic gene expression changes arising from mature microglia. Unbiased RNA-Seq profiling was used to identify gene expression changes in isolated prefrontal cortical microglia in response to recurring bouts of voluntary alcohol drinking behavior. The voluntary ethanol paradigm utilizes long-term consumption ethanol that results in escalated alcohol intake and altered cortical plasticity that is seen in humans. Gene coexpression analysis identified a coordinately regulated group of genes, unique to microglia, that collectively are associated with alcohol consumption. Genes within this group are involved in toll-like receptor signaling and transforming growth factor beta signaling. Network connectivity of this group identified Siglech as a putative hub gene and highlighted the potential importance of proteases in the microglial response to chronic ethanol. In conclusion, we identified a distinctive microglial gene expression signature for neuroimmune responses related to alcohol consumption that provides valuable insight into microglia-specific changes underlying the development of substance abuse, and possibly other CNS disorders.

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“…The research here suggests the possibility that activated microglia protect against tumours by 'stressing' the cancer cells and then phagocytosing these cells. And this is supported by evidence that microglia can phagocytose live glioma cells (Kopatz et al, 2013). However, it would be important to determine whether phagocytosis can protect against brain tumours in vivo.…”

Section: Discussionmentioning

confidence: 96%

Activated microglia cause reversible apoptosis of pheochromocytoma cells, inducing their cell death by phagocytosis

Hornik

Vilalta

Brown

2016

Journal of Cell Science

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Some apoptotic processes, such as phosphatidylserine exposure, are potentially reversible and do not necessarily lead to cell death. However, phosphatidylserine exposure can induce phagocytosis of a cell, resulting in cell death by phagocytosis: phagoptosis. Phagoptosis of neurons by microglia might contribute to neuropathology, whereas phagoptosis of tumour cells by macrophages might limit cancer. Here, we examined the mechanisms by which BV-2 microglia killed co-cultured pheochromocytoma (PC12) cells that were either undifferentiated or differentiated into neuronal cells. We found that microglia activated by lipopolysaccharide rapidly phagocytosed PC12 cells. Activated microglia caused reversible phosphatidylserine exposure on and reversible caspase activation in PC12 cells, and caspase inhibition prevented phosphatidylserine exposur and decreased subsequent phagocytosis. Nitric oxide was necessary and sufficient to induce the reversible phosphatidylserine exposure and phagocytosis. The PC12 cells were not dead at the time they were phagocytised, and inhibition of their phagocytosis left viable cells. Cell loss was inhibited by blocking phagocytosis mediated by phosphatidylserine, MFG-E8, vitronectin receptors or P2Y 6 receptors. Thus, activated microglia can induce reversible apoptosis of target cells, which is insufficient to cause apoptotic cell death, but sufficient to induce their phagocytosis and therefore cell death by phagoptosis.

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Siglec‐h on activated microglia for recognition and engulfment of glioma cells

Cited by 68 publications

References 42 publications

Cell Depletion in Mice That Express Diphtheria Toxin Receptor under the Control of SiglecH Encompasses More Than Plasmacytoid Dendritic Cells

Cell Depletion in Mice That Express Diphtheria Toxin Receptor under the Control of SiglecH Encompasses More Than Plasmacytoid Dendritic Cells

Microglial-specific transcriptome changes following chronic alcohol consumption

Activated microglia cause reversible apoptosis of pheochromocytoma cells, inducing their cell death by phagocytosis

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