TLR2 controls random motility, while TLR7 regulates chemotaxis of microglial cells via distinct pathways

Ifuku, Masataka; Buonfiglioli, Alice; Jordan, Philipp; Lehnardt, Seija; Kettenmann, Helmut

doi:10.1016/j.bbi.2016.08.003

Cited by 26 publications

(23 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A substantial part of the sensome is accounted for by pattern recognition receptors (25%), such as the Toll-like receptors (TLRs) which recognize conserved motifs of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), molecular fragments released from necrotic or dying cells. Stimulation of TLRs causes induction of AP-1 and NF-κB and subsequent activation of multiple pro-inflammatory genes, as well as profound changes in morphology and migratory behavior [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Imaging of Microglial Calcium Signaling in Brain Inflammation and Injury

Tvrdík

Kalani

2017

IJMS

View full text Add to dashboard Cite

Microglia, the innate immune sentinels of the central nervous system, are the most dynamic cells in the brain parenchyma. They are the first responders to insult and mediate neuroinflammation. Following cellular damage, microglia extend their processes towards the lesion, modify their morphology, release cytokines and other mediators, and eventually migrate towards the damaged area and remove cellular debris by phagocytosis. Intracellular Ca2+ signaling plays important roles in many of these functions. However, Ca2+ in microglia has not been systematically studied in vivo. Here we review recent findings using genetically encoded Ca2+ indicators and two-photon imaging, which have enabled new insights into Ca2+ dynamics and signaling pathways in large populations of microglia in vivo. These new approaches will help to evaluate pre-clinical interventions and immunomodulation for pathological brain conditions such as stroke and neurodegenerative diseases.

show abstract

Section: Introductionmentioning

confidence: 99%

In Vivo Imaging of Microglial Calcium Signaling in Brain Inflammation and Injury

Tvrdík

Kalani

2017

IJMS

View full text Add to dashboard Cite

show abstract

“…As LIF is known to be protective and expressed in Müller cells, microglia are likely acting as an intermediate in the induction of Müller cell protective responses. Indeed, it has been shown that microglial mobility depends in part on TLR2 49 . One explanation to our data showing that TLR2 −/− male mice have reduced formation of amoeboid cells, is that microglia have an impaired ability to move toward areas of stress (i.e.…”

Section: Discussionmentioning

confidence: 99%

Damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner

Hooper

Wang

Browning

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Retinal degeneration is a common cause of irreversible blindness and is caused by the death of retinal light-sensitive neurons called photoreceptors. At the onset of degeneration, stressed photoreceptors cause retinal glial cells to secrete neuroprotective factors that slow the pace of degeneration. Leukemia inhibitory factor (LIF) is one such factor that is required for endogenous neuroprotection. Photoreceptors are known to release signals of cellular stress, called damage-associated molecular patterns (DAMPs) early in degeneration, and we hypothesized that receptors for DAMPs or pattern recognition receptors (PRRs) play a key role in the induction of LIF and neuroprotective stress responses in retinal glial cells. Toll-like receptor 2 (TLR2) is a well-established DAMP receptor. In our experiments, activation of TLR2 protected both male and female mice from light damage, while the loss of TLR2 in female mice did not impact photoreceptor survival. In contrast, induction of protective stress responses, microglial phenotype and photoreceptor survival were strongly impacted in male TLR2−/− mice. Lastly, using publicly available gene expression data, we show that TLR2 is expressed highly in resting microglia prior to injury, but is also induced in Müller cells in inherited retinal degeneration.

show abstract

“…The two treatments differentially affected genes encoding molecular links between the axon guidance pathway, TLR pathway, and microglial mobility. Tlr7 regulates microglial chemotaxis, with Rac1 as its effector (Ifuku, Buonfiglioli, Jordan, Lehnardt, & Kettenmann, 2016). Rac1 has also been characterized as a Tlr4 target in the context of M1/M2 microglia polarization (Yao et al, 2017).…”

Section: Genes Classified By Expression Specificity Display Distincmentioning

confidence: 99%

Open chromatin landscape of rat microglia upon proinvasive or inflammatory polarization

Przanowski

Mondal

Cabaj

et al. 2019

Glia

View full text Add to dashboard Cite

Microglia are brain‐resident, myeloid cells that play important roles in health and brain pathologies. Herein, we report a comprehensive, replicated, false discovery rate‐controlled dataset of DNase‐hypersensitive (DHS) open chromatin regions for rat microglia. We compared the open chromatin landscapes in untreated primary microglial cultures and cultures stimulated for 6 hr with either glioma‐conditioned medium (GCM) or lipopolysaccharide (LPS). Glioma‐secreted factors induce proinvasive and immunosuppressive activation of microglia, and these cells then promote tumor growth. The open chromatin landscape of the rat microglia consisted of 126,640 reproducible DHS regions, among which 2,303 and 12,357 showed a significant change in openness following stimulation with GCM or LPS, respectively. Active genes exhibited constitutively open promoters, but there was no direct dependence between the aggregated openness of DHS regions near a gene and its expression. Individual regions mapped to the same gene often presented different patterns of openness changes. GCM‐regulated DHS regions were more frequent in areas away from gene bodies, while LPS‐regulated regions were more frequent in introns. GCM and LPS differentially affected the openness of regions mapped to immune checkpoint genes. The two treatments differentially affected the aggregated openness of regions mapped to genes in the Toll‐like receptor signaling and axon guidance pathways, suggesting that the molecular machinery used by migrating microglia is similar to that of growing axons and that modulation of these pathways is instrumental in the induction of proinvasive polarization of microglia by glioma. Our dataset of open chromatin regions paves the way for studies of gene regulation in rat microglia.

show abstract

TLR2 controls random motility, while TLR7 regulates chemotaxis of microglial cells via distinct pathways

Cited by 26 publications

References 60 publications

In Vivo Imaging of Microglial Calcium Signaling in Brain Inflammation and Injury

In Vivo Imaging of Microglial Calcium Signaling in Brain Inflammation and Injury

Damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner

Open chromatin landscape of rat microglia upon proinvasive or inflammatory polarization

Contact Info

Product

Resources

About