scholarly journals Age-Dependent Microglial Response to Systemic Infection

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1037
Author(s):  
Brianna Cyr ◽  
Juan Pablo de Rivero Vaccari
Keyword(s):  
Escherichia Coli ◽  
Recent Article ◽  
Aging Process ◽  
Inflammatory Responses ◽  
Systemic Infection ◽  
Innate Immune ◽  
Older Individuals ◽  
Age Dependent ◽  
Microglial Response ◽  
The Brain

Inflammation is part of the aging process, and the inflammatory innate immune response is more exacerbated in older individuals when compared to younger individuals. Similarly, there is a difference in the response to systemic infection that varies with age. In a recent article by Hoogland et al., the authors studied the microglial response to systemic infection in young (2 months) and middle-aged mice (13–14 months) that were challenged with live Escherichia coli to investigate whether the pro- and anti-inflammatory responses mounted by microglia after systemic infection varies with age. Here, we comment on this study and its implications on how inflammation in the brain varies with age.

scholarly journals Aging and Microglial Response following Systemic Stimulation with Escherichia coli in Mice

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 279
Author(s):  
Inge C.M. Hoogland ◽  
Dunja Westhoff ◽  
Joo-Yeon Engelen-Lee ◽  
Mercedes Valls Seron ◽  
Judith H.M.P. Houben-Weerts ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Flow Cytometry ◽  
Inflammatory Response ◽  
Middle Aged ◽  
E Coli ◽  
Age Dependent ◽  
Live Bacteria ◽  
Microglial Response ◽  
The Brain ◽  
Systemic Compartment

Systemic infection is an important risk factor for the development cognitive impairment and neurodegeneration in older people. Animal experiments show that systemic challenges with live bacteria cause a neuro-inflammatory response, but the effect of age on this response in these models is unknown. Young (2 months) and middle-aged mice (13–14 months) were intraperitoneally challenged with live Escherichia coli (E. coli) or saline. The mice were sacrificed at 2, 3 and 7 days after inoculation; for all time points, the mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h after inoculation. Microglial response was monitored by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry, and inflammatory response by mRNA expression of pro- and anti-inflammatory mediators. We observed an increased microglial cell number and moderate morphologically activated microglial cells in middle-aged mice, as compared to young mice, after intraperitoneal challenge with live E. coli. Flow cytometry of microglial cells showed higher CD45 and CD11b expressions in middle-aged infected mice compared to young infected mice. The brain expression levels of pro-inflammatory genes were higher in middle-aged than in young infected mice, while middle-aged infected mice had similar expression levels of these genes in the systemic compartment. We conclude that systemic challenge with live bacteria causes an age-dependent neuro-inflammatory and microglial response. Our data show signs of an age-dependent disconnection of the inflammatory transcriptional signature between the brain and the systemic compartment.

scholarly journals Gut–neuroimmune interactions: the unexpected role of the immune system in brain development

2019 ◽  
Vol 41 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Simon Spichak ◽  
Timothy G. Dinan ◽  
John F. Cryan
Keyword(s):  
Immune System ◽  
Brain Development ◽  
Neuronal Development ◽  
Inflammatory Responses ◽  
Later Life ◽  
Innate Immune ◽  
Brain Health ◽  
Cytokines And Chemokines ◽  
The Brain

How does the immune system impact brain development? The exciting and somewhat unexpected relationship between the immune system and the brain has become one of the most fascinating topics in neuroscience. Even though the immune system was initially implicated in resolving viral and bacterial threats, it is now becoming more evident that it also plays a role in processes in the brain, both under healthy and pathological conditions. This novel role of the immune system in brain health has been implicated in various psychopathologies where neurodevelopment, stress and mood are central. In particular, its role in healthy brain development is becoming more evident, and understanding neuroimmune communication is becoming crucial in treating neurodevelopmental and mood disorders in later life. In the brain, glia function as part of the innate immune system and are programmed to respond to pathogens and physical injury. They also play an important role in neuronal development and pruning. These cells communicate with and respond to chemical signals, such as cytokines and chemokines, which can then initiate or downregulate inflammatory responses. Finally, the trillions of microbes residing in the gut can also stimulate cytokine and chemokine responses in the periphery and play an important role in both immunity and brain development.

scholarly journals Ovarian steroids do not affect bovine endometrial cytokine or chemokine responses to Escherichia coli or LPS in vitro

Reproduction ◽  
2014 ◽  
Vol 148 (6) ◽  
pp. 593-606 ◽  
Author(s):  
João P E Saut ◽  
Gareth D Healey ◽  
Alan M Borges ◽  
I Martin Sheldon
Keyword(s):  
Escherichia Coli ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Ovarian Cycle ◽  
Innate Immune ◽  
Uterine Disease ◽  
Ovarian Steroids ◽  
E Coli

The risk of bacterial infection of the endometrium causing uterine disease in cattle is increased in the progesterone-dominated luteal phase of the ovarian cycle, while oestrogens or oestrus are therapeutic or protective against disease. The first line of defence against bacteria, such as Escherichia coli that cause inflammation of the endometrium, is the innate immune system, which recognises bacterial lipopolysaccharide (LPS). This study tested the hypothesis that cyclic variation in ovarian hormone concentrations alters innate immune responses within the bovine endometrium. Ex vivo organ cultures of endometrium, and in vitro cultures of endometrial epithelial and stromal cells, and peripheral blood mononuclear cells (PBMCs), all mounted inflammatory responses to E. coli or LPS, with secretion of inflammatory mediators interleukin 1β (IL1β), IL6 and IL8, and increased expression of mRNA encoding IL1B, IL6, CXCL8 (IL8) and CCL5. However, these inflammatory responses, typical of innate immunity, were not affected by the stage of ovarian cycle in which the endometrium was collected for organ culture, or by exogenous oestradiol or progesterone. Although a dexamethasone-positive control reduced inflammation stimulated by E. coli or LPS, treatment with oestradiol or progesterone, or inhibitors of oestradiol or progesterone nuclear receptors, did not affect endometrial cell or PBMC secretion of IL1β, IL6 or IL8, or IL1B, IL6, CXCL8 and CCL5 gene expression. In conclusion, the stage of the oestrus cycle or ovarian steroids did not modulate the innate immune response in the bovine endometrium in vitro.

scholarly journals Macropinosomes host TLR9 signaling and regulation of inflammatory responses in microglia

2021 ◽  
Author(s):  
Yu Hung ◽  
Neeraj Tuladhar ◽  
Zhi-jian Xiao ◽  
Samuel J Tong ◽  
Jana Vukovic ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Fluid Phase ◽  
Innate Immune ◽  
Acid Activation ◽  
Cpg Dna ◽  
Inflammatory Cytokine Production ◽  
Intracellular Receptor ◽  
The Brain ◽  
Anti Inflammatory Cytokine ◽  
Tlr9 Signaling

AbstractTo support their innate immune and scavenging functions in the brain, microglia are equipped with Toll-like receptors (TLRs), including the intracellular receptor TLR9, which is activated by microbial CpG-rich DNA. Macropinocytosis is an abundant and inducible pathway in microglia for fluid-phase uptake and ingestion of microbes and cell debris. TLR9 signaling has been ascribed to endolysosomes, particularly lysosomes, which it accesses through direct transport or via internalization from the surface. Here, TLR9 and exogenous CpG-DNA are localized during uptake into fluid-filled macropinosomes, upon upregulated macropinocytosis, where acidic and proteolytic environments support MyD88-induced signaling. Macropinosomes represent an abundant pathway for endolysosomal traffic of TLR9 but are also a much more exposed site for nucleic acid activation of the receptor with a risk of excessive inflammation. To constrain TLR9 inflammation, macropinosomes also house the TLR9 co-receptor LRP1 and regulators Rab8a and PI3Kγ which augment Akt signaling and favor anti-inflammatory cytokine production. Macropinosomes and their inflammatory regulators are therefore important components of TLR9 pathways in microglia that are poised for surveillance and protection in the CNS.

scholarly journals Long Non-coding Antisense RNA DDIT4-AS1 Regulates Meningitic Escherichia coli-Induced Neuroinflammation by Promoting DDIT4 mRNA Stability

2022 ◽  
Author(s):  
Bo Yang ◽  
Bojie Xu ◽  
Ruicheng Yang ◽  
Jiyang Fu ◽  
Liang Li ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Inflammatory Responses ◽  
Expression Patterns ◽  
Therapeutic Interventions ◽  
E Coli ◽  
Protein Levels ◽  
Wide Range ◽  
The Stability ◽  
Duplex Formation ◽  
The Brain

AbstractOur previous studies have shown that meningitic Escherichia coli can colonize the brain and cause neuroinflammation. Controlling the balance of inflammatory responses in the host central nervous system is particularly vital. Emerging evidence has shown the important regulatory roles of long non-coding RNAs (lncRNAs) in a wide range of biological and pathological processes. However, whether lncRNAs participate in the regulation of meningitic E. coli-mediated neuroinflammation remains unknown. In the present study, we characterized a cytoplasm-enriched antisense lncRNA DDIT4-AS1, which showed similar concordant expression patterns with its parental mRNA DDIT4 upon E. coli infection. DDIT4-AS1 modulated DDIT4 expression at both mRNA and protein levels. Mechanistically, DDIT4-AS1 promoted the stability of DDIT4 mRNA through RNA duplex formation. DDIT4-AS1 knockdown and DDIT4 knockout both attenuated E. coli-induced NF-κB signaling as well as pro-inflammatory cytokines expression, and DDIT4-AS1 regulated the inflammatory response by targeting DDIT4. In summary, our results show that DDIT4-AS1 promotes E. coli-induced neuroinflammatory responses by enhancing the stability of DDIT4 mRNA through RNA duplex formation, providing potential nucleic acid targets for new therapeutic interventions in the treatment of bacterial meningitis.

scholarly journals Biomarkers for Microglial Activation in Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Ronald Lautner ◽  
Niklas Mattsson ◽  
Michael Schöll ◽  
Kristin Augutis ◽  
Kaj Blennow ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microglial Activation ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
First Line ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
The Brain ◽  
Neuroimaging Techniques

Intensive research over the last decades has provided increasing evidence for neuroinflammation as an integral part in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Inflammatory responses in the central nervous system (CNS) are initiated by activated microglia, representing the first line of the innate immune defence of the brain. Therefore, biochemical markers of microglial activation may help us understand the underlying mechanisms of neuroinflammation in AD as well as the double-sided qualities of microglia, namely, neuroprotection and neurotoxicity. In this paper we summarize candidate biomarkers of microglial activation in AD along with a survey of recent neuroimaging techniques.

scholarly journals Trimming Surface Sugars Protects Histoplasma from Immune Attack

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Gordon D. Brown
Keyword(s):  
Cell Walls ◽  
Fungal Pathogens ◽  
Recent Article ◽  
Histoplasma Capsulatum ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Immune Recognition ◽  
Fungal Cell ◽  
Immune Attack ◽  
Fungal Cell Walls

ABSTRACT Dectin-1 is an essential innate immune receptor that recognizes β-glucans in fungal cell walls. Its importance is underscored by the mechanisms that fungal pathogens have evolved to avoid detection by this receptor. One such pathogen is Histoplasma capsulatum , and in a recent article in mBio , Rappleye’s group presented data showing that yeasts of this organism secrete a β-glucanase, Eng1, which acts to prune β-glucans that are exposed on the fungal cell surface [A. L. Garfoot et al., mBio 7(2):e01388-15, 2016, http://dx.doi.org/10.1128/mBio.01388-15 ]. The trimming of these sugars reduces immune recognition through Dectin-1 and subsequent inflammatory responses, enhancing the pathogenesis of H. capsulatum .

scholarly journals Safety profile of the transcription factor EB (TFEB)-based gene therapy through intracranial injection in mice

2020 ◽  
Vol 11 (1) ◽  
pp. 241-250
Author(s):  
Zhenyu Li ◽  
Guangqian Ding ◽  
Yudi Wang ◽  
Zelong Zheng ◽  
Jianping Lv
Keyword(s):  
Gene Therapy ◽  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
Brain Tissue ◽  
Inflammatory Responses ◽  
Tissue Samples ◽  
Protein Levels ◽  
Virus Serotype ◽  
Transcription Factor Eb ◽  
The Brain

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.

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