Microglial Activation After Systemic Stimulation With Lipopolysaccharide and Escherichia coli

Hoogland, Inge C.M.; Westhoff, Dunja; Engelen-Lee, Joo-Yeon; Melief, Jeroen; Serón, Mercedes Valls; Houben-Weerts, Judith H. M. P.; Huitinga, Inge; Westerloo, David J. van; Poll, Tom van der; Gool, Willem A. van; Beek, Diederik van de

doi:10.3389/fncel.2018.00110

Cited by 67 publications

(51 citation statements)

References 16 publications

(27 reference statements)

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“…Olfactory bulb CD11c‐eYFP + Iba‐1 + microglia and CD11c‐eYFP − Iba‐1 + microglia displayed an “activated” morphology 24 and 48 hr post‐LPS injection, whereas cortical microglia populations retained their classical ramified morphology at all examined time points according to Sholl analysis parameters. These findings contrast with previous studies in male C57Bl/6 J mice, which reported that a single intraperitoneal injection of LPS (5 mg/kg) resulted in morphological “activation” of cortical microglia at either 3 hr (Qin et al, ) or 48 hr post‐LPS injection (Hoogland et al, ). Our study differed from these previous reports as we utilized: (a) a different dose of LPS; (b) mice of both sexes; and (c) transgenic mice on a mixed genetic background.…”

Section: Discussioncontrasting

confidence: 99%

Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges

Dando

Kazanis

Chinnery

et al. 2018

Glia

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The central nervous system (CNS) is considered to be immune privileged, owing in part to the absence of major histocompatibility (MHC) class II + cells in the healthy brain parenchyma. However, systemic inflammation can activate microglia to express MHC class II, suggesting that systemic inflammation may be sufficient to mature microglia into functional antigen presenting cells (APCs). We examined the effects of systemic lipopolysaccharide (LPS)-induced inflammation on the phenotype and function of putative APCs within the mouse brain parenchyma, as well as its supporting tissues-the choroid plexus and meninges. Microglia isolated from different regions of the brain demonstrated significant heterogeneity in their ability to present antigen to naïve OT-II CD4 + T cells following exposure to systemic LPS. Olfactory bulb microglia (but not cortical microglia) intimately interacted with T cells in vivo and stimulated T cell proliferation in vitro, albeit in the absence of co-stimulation. In contrast, myeloid cells within the choroid plexus and meninges were immunogenic and upregulated the co-stimulatory molecule CD80 following systemic inflammation. Dural APCs, which clustered around LYVE-1 + lymphatics, were more efficient at stimulating naïve T cell proliferation than choroid plexus APCs, suggesting that the dura may be an underappreciated site for immune interactions. This study has highlighted the functional diversity of myeloid cells within the sub-compartments of the CNS and its supporting tissues. Furthermore, these findings demonstrate that systemic inflammation can mature selected microglia populations and choroid plexus/meningeal myeloid cells into functional APCs, which may contribute to the pathogenesis of neuroinflammation and neurodegenerative diseases. K E Y W O R D Santigen presenting cells, brain parenchyma, central nervous system, meninges, microglia

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Section: Discussioncontrasting

confidence: 99%

Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges

Dando

Kazanis

Chinnery

et al. 2018

Glia

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“…They found that compared with control mice, mice infected with live E. coli have microglial activation by 72 h post-inoculation. Using flow cytometry analysis, they also found that by 72 h, microglia from E. coli-infected mice had increases in mean cell size and CD45 expression, compared with the controls [41]. Mayer et al's results suggested that V. vulnificus MO6-24/O lipopolysaccharide activates rat microglia in vitro and stimulates the release of superoxide anion in vivo [42].…”

Section: Discussionmentioning

confidence: 97%

“…Microglia recognize many Gram-negative pathogenic bacteria that can colonize the central nervous system [39]. In addition to P. aeruginosa, Escherichia coli and Vibrio vulnificus have effects on microglial cells [40][41][42]. Hoogland et al developed a live E. coli mouse model that mimics the delirium-associated infection [41].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to P. aeruginosa, Escherichia coli and Vibrio vulnificus have effects on microglial cells [40][41][42]. Hoogland et al developed a live E. coli mouse model that mimics the delirium-associated infection [41]. They found that compared with control mice, mice infected with live E. coli have microglial activation by 72 h post-inoculation.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Pseudomonas aeruginosa on Microglial-Derived Extracellular Vesicle Biogenesis and Composition

et al. 2019

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The packaging of molecular constituents inside extracellular vesicles (EVs) allows them to participate in intercellular communication and the transfer of biological molecules, however the role of EVs during bacterial infection is poorly understood. The goal of this study was to examine the effects of Pseudomonas aeruginosa (P. aeruginosa) infection on the biogenesis and composition of EVs derived from the mouse microglia cell line, BV-2. BV-2 cells were cultured in exosome-free media and infected with 0, 1.3 × 104, or 2.6 × 104 colony forming units per milliliter P. aeruginosa for 72 h. The results indicated that compared with the control group, BV-2 cell viability significantly decreased after P. aeruginosa infection and BV-2-derived EVs concentration decreased significantly in the P. aeruginosa-infected group. P. aeruginosa infection significantly decreased chemokine ligand 4 messenger RNA in BV-2-derived infected EVs, compared with the control group (p ≤ 0.05). This study also revealed that heat shock protein 70 (p ≤ 0.05) and heat shock protein 90β (p ≤ 0.001) levels of expression within EVs increased after P. aeruginosa infection. EV treatment with EVs derived from P. aeruginosa infection reduced cell viability of BV-2 cells. P. aeruginosa infection alters the expression of specific proteins and mRNA in EVs. Our study suggests that P. aeruginosa infection modulates EV biogenesis and composition, which may influence bacterial pathogenesis and infection.

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“…As we previously described that ocellatins decrease ROS on mice hippocampi, we analysed the effect of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) on LPS-induced NF-kB activation. Experimental studies show that stimulation by LPS induces microglial activation 37 . When microglia activated, they release several factors, such as ROS, and are capable of activate NF-kB transcription factor.…”

Section: Discussionmentioning

confidence: 99%

Novel Ocellatin Peptides Mitigate LPS-induced ROS Formation and NF-kB Activation in Microglia and Hippocampal Neurons

Sousa

Oliveira

et al. 2020

Sci Rep

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cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. the peptides obtained possessed the amino acid sequences, GVVDiLKGAAKDLAGH and GVVDiLKGAAKDLAGHLASKV, with monoisotopic masses of [M + H] ± = 1563.8 Da and [M + H] ± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and nf-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. these functional properties suggest possible to neuromodulatory therapeutic applications.The skin of amphibians has been the subject of interest and study of several research groups as well as pharmaceutical industries, due to the abundance and diversity of bioactive molecules with potential biotechnological applications, especially for the production of new drugs 1 . The characteristic way of living of amphibians is divided between aquatic and the terrestrial environment 2 . They possess a highly sensitive skin that is essential to its respiration and is highly vulnerable to environmental aggressions, such as desiccation, attack of microorganisms, ultraviolet radiation, and injuries 3 . This vulnerability has culminated in the development of an innate defense system as a survival strategy based on the expression, production, accumulation, and secretion of bioactive www.nature.com/scientificreports www.nature.com/scientificreports/ against E. coli with MIC of 125 μg/mL (Fig. 4) and inhibition percentage corresponding to 34.17 ± 11.66%. The optical density (630 nm) of E. coli decreased in a dose-dependent manner, showing significant reduction on viability for both the ocellatins at concentrations between 125 and 1000 μg/mL. The value 125 μg/mL of MIC is too high to be characterized as having significant antibacterial potential. Moreover, only Ocellatin-K1(1-16) showed any significant activity against S. aureus featuring MICs of 31.25 μg/mL and inhibition percentage corresponding to 30.79 ± 10.27%. This activity was not seen to be conc...

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Microglial Activation After Systemic Stimulation With Lipopolysaccharide and Escherichia coli

Cited by 67 publications

References 16 publications

Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges

Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges

Effects of Pseudomonas aeruginosa on Microglial-Derived Extracellular Vesicle Biogenesis and Composition

Novel Ocellatin Peptides Mitigate LPS-induced ROS Formation and NF-kB Activation in Microglia and Hippocampal Neurons

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