scholarly journals ApoE facilitates the microglial response to amyloid plaque pathology

2018 ◽  
Vol 215 (4) ◽  
pp. 1047-1058 ◽  
Author(s):  
Jason D. Ulrich ◽  
Tyler K. Ulland ◽  
Thomas E. Mahan ◽  
Sofie Nyström ◽  
K. Peter Nilsson ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Amyloid Β ◽  
Amyloid Plaque ◽  
Innate Immune ◽  
Fluorescent Imaging ◽  
Amyloid Pathology ◽  
Plaque Deposition ◽  
The Impact ◽  
Deficient Mice

One of the hallmarks of Alzheimer’s disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-β (Aβ) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aβ in the brain. In addition to influencing Aβ metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1ΔE9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aβ morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque–associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.

scholarly journals Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Gopu Sriram ◽  
Vaishali Prakash Natu ◽  
Intekhab Islam ◽  
Xin Fu ◽  
Chaminda Jayampath Seneviratne ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Mesenchymal Stem Cells ◽  
Innate Immune Response ◽  
Embryonic Stem ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Multipotent Stem Cells ◽  
Cytokine Expression Profile ◽  
The Impact

Periodontitis involves complex interplay of bacteria and host immune response resulting in destruction of supporting tissues of the tooth. Toll-like receptors (TLRs) play a role in recognizing microbial pathogens and eliciting an innate immune response. Recently, the potential application of multipotent stem cells and pluripotent stem cells including human embryonic stem cells (hESCs) in periodontal regenerative therapy has been proposed. However, little is known about the impact of periodontopathogens on hESC-derived progenies. This study investigates the effects of heat-killed periodontopathogens, namely,Porphyromonas gingivalisandAggregatibacter actinomycetemcomitans, on TLR and cytokine expression profile of hESC-derived progenies, namely, fibroblasts (hESC-Fib) and mesenchymal stem cells (hESC-MSCs). Additionally, the serotype-dependent effect ofA. actinomycetemcomitanson hESC-derived progenies was explored. Both hESC-Fib and hESC-MSCs constitutively expressedTLR-2andTLR-4. hESC-Fib upon exposure to periodontopathogens displayed upregulation of TLRs and release of cytokines (IL-1β, IL-6, and IL-8). In contrast, hESC-MSCs were largely nonresponsive to bacterial challenge, especially in terms of cytokine production. Further, exposure of hESC-Fib toA. actinomycetemcomitansserotype c was associated with higher IL-8 production than serotype b. In contrast, the hESC-MSCs displayed no serotype-dependent response. Differential response of the two hESC progenies implies a phenotype-dependent response to periodontopathogens and supports the concept of immunomodulatory properties of MSCs.

scholarly journals The NALP3 inflammasome is involved in the innate immune response to amyloid-β

2008 ◽  
Vol 9 (8) ◽  
pp. 857-865 ◽  
Author(s):  
Annett Halle ◽  
Veit Hornung ◽  
Gabor C Petzold ◽  
Cameron R Stewart ◽  
Brian G Monks ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Amyloid Β ◽  
Innate Immune ◽  
Nalp3 Inflammasome

scholarly journals The impact of vitamin D on the innate immune response to uropathogenic Escherichia coli during pregnancy

2015 ◽  
Vol 21 (5) ◽  
pp. 482.e1-482.e7 ◽  
Author(s):  
N.L. Ramos ◽  
M. Sekikubo ◽  
F. Kironde ◽  
F. Mirembe ◽  
M. Sääf ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Vitamin D ◽  
Immune Response ◽  
Innate Immune Response ◽  
Uropathogenic Escherichia Coli ◽  
Innate Immune ◽  
The Impact

scholarly journals The SUMOylation of TAB2 mediated by TRIM60 inhibits MAPK/NF-κB activation and the innate immune response

2020 ◽  
Author(s):  
Zhiwen Gu ◽  
Xueying Chen ◽  
Wenyong Yang ◽  
Yu Qi ◽  
Hui Yu ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Posttranslational Modifications ◽  
Innate Immune ◽  
Pathogen Invasion ◽  
In Vivo Experiments ◽  
New Strategy ◽  
Deficient Mice

Abstract Activation of the TAK1 signalosome is crucial for mediating the innate immune response to pathogen invasion and is regulated by multiple layers of posttranslational modifications, including ubiquitination, SUMOylation, and phosphorylation; however, the underlying molecular mechanism is not fully understood. In this study, TRIM60 negatively regulated the formation and activation of the TAK1 signalosome. Deficiency of TRIM60 in macrophages led to enhanced MAPK and NF-κB activation, accompanied by elevated levels of proinflammatory cytokines but not IFN-I. Immunoprecipitation-mass spectrometry assays identified TAB2 as the target of TRIM60 for SUMOylation rather than ubiquitination, resulting in impaired formation of the TRAF6/TAB2/TAK1 complex and downstream MAPK and NF-κB pathways. The SUMOylation sites of TAB2 mediated by TRIM60 were identified as K329 and K562; substitution of these lysines with arginines abolished the SUMOylation of TAB2. In vivo experiments showed that TRIM60-deficient mice showed an elevated immune response to LPS-induced septic shock and L. monocytogenes infection. Our data reveal that SUMOylation of TAB2 mediated by TRIM60 is a novel mechanism for regulating the innate immune response, potentially paving the way for a new strategy to control antibacterial immune responses.

scholarly journals The role of the E2F1 transcription factor in the innate immune response to systemic LPS

2012 ◽  
Vol 303 (5) ◽  
pp. L391-L400 ◽  
Author(s):  
Laura A. Warg ◽  
Judy L. Oakes ◽  
Rachel Burton ◽  
Amanda J. Neidermyer ◽  
Holly R. Rutledge ◽  
...  
Keyword(s):  
Immune Response ◽  
Transcription Factor ◽  
Inflammatory Response ◽  
Innate Immune Response ◽  
Liver Tissue ◽  
Innate Immune ◽  
Coagulation Cascade ◽  
Mirna Profiling ◽  
Mrna Targets ◽  
Deficient Mice

Previous publications from our and other groups identified E2F1 as a transcription factor involved in the regulation of inflammatory response to Toll-like receptor ligands including LPS. In this study, we challenged E2F1-deficient mice with LPS systemically and demonstrated decreased survival despite attenuated inflammatory response compared with controls. Gene expression profiling of liver tissue identified a dampened transcriptional response in the coagulation cascade in B6;129E2F1−/− compared with B6x129 F2 mice. These data were further corroborated by increased prothrombin time, activated partial thromboplastin time, and fibrin split products in the blood of E2F1-deficient mice, suggesting disseminated intravascular coagulation as a consequence of uncontrolled sepsis providing at least a partial explanation for their decreased survival despite attenuated inflammatory response. To identify novel miRNAs involved in the innate immune response to LPS, we also performed miRNA profiling of liver tissue from B6;129E2F1−/− and B6x129 F2 mice treated with LPS systemically. Our analysis identified a set of miRNAs and their mRNA targets that are significantly differentially regulated in E2F1-deficient but not control mice including let-7g, miR-101b, miR-181b, and miR-455. These miRNAs represent novel regulators of the innate immune response. In summary, we used transcriptional and miRNA profiling to characterize the response of E2F1-deficient mice to systemic LPS.

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