scholarly journals Erratum to “Hydroxychloroquine Effects on TLR Signalling: Underexposed but Unneglectable in COVID-19”

2021 ◽  
Vol 2021 ◽  
pp. 1-2
Author(s):  
Aliede E. in ‘t Veld ◽  
Manon A. A. Jansen ◽  
Luuk C. A. Ciere ◽  
Matthijs Moerland
Keyword(s):  
Tlr Signalling

scholarly journals Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
R. Ved ◽  
F. Sharouf ◽  
B. Harari ◽  
M. Muzaffar ◽  
S. Manivannan ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Culture Medium ◽  
Traumatic Injury ◽  
High Mobility ◽  
Oligodendrocyte Progenitor Cells ◽  
Therapeutic Approaches ◽  
Mature Oligodendrocyte ◽  
Oligodendrocyte Progenitor ◽  
Tlr Signalling

AbstractTraumatic brain injury (TBI) is associated with poor clinical outcomes; autopsy studies of TBI victims demonstrate significant oligodendrocyte progenitor cell (OPC) death post TBI; an observation, which may explain the lack of meaningful repair of injured axons. Whilst high-mobility group box-1 (HMGB1) and its key receptors TLR2/4 are identified as key initiators of neuroinflammation post-TBI, they have been identified as attractive targets for development of novel therapeutic approaches to improve post-TBI clinical outcomes. In this report we establish unequivocal evidence that HMGB1 released in vitro impairs OPC response to mechanical injury; an effect that is pharmacologically reversible. We show that needle scratch injury hyper-acutely induced microglial HMGB1 nucleus-to-cytoplasm translocation and subsequent release into culture medium. Application of injury-conditioned media resulted in significant decreases in OPC number through anti-proliferative effects. This effect was reversed by co-treatment with the TLR2/4 receptor antagonist BoxA. Furthermore, whilst injury conditioned medium drove OPCs towards an activated reactive morphology, this was also abolished after BoxA co-treatment. We conclude that HMGB1, through TLR2/4 dependant mechanisms, may be detrimental to OPC proliferation following injury in vitro, negatively affecting the potential for restoring a mature oligodendrocyte population, and subsequent axonal remyelination. Further study is required to assess how HMGB1-TLR signalling influences OPC maturation and myelination capacity.

scholarly journals Differential TLR signalling

2004 ◽  
Vol 4 (1) ◽  
pp. 3-3
Author(s):  
Elaine Bell
Keyword(s):  
Tlr Signalling

scholarly journals Innate Immune Response as a New Challenge in Periodontal Inflammation

2021 ◽  
Author(s):  
Ana Marina Andrei ◽  
Elena Cristina Andrei ◽  
Elena Camelia Stănciulescu ◽  
Mihaela Cezarina Mehedinți ◽  
Mihaela Jana Țuculină ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Periodontal Diseases ◽  
Bacterial Species ◽  
Innate Immune ◽  
Beneficial Effects ◽  
Periodontal Tissues ◽  
Periodontal Inflammation ◽  
Genetic And Environmental Factors ◽  
Tlr Signalling

Gingivitis and periodontitis are induced by numerous pathogenic microbiota hosted in the subgingival biofilm that first trigger the innate immune response. Innate immune response is part of a homeostatic system which is the first line defence and defines the host inherited resistance to infection. Both genetic and environmental factors are involved in variable individual susceptibility to inflammation of periodontal tissues. That is why, although more than 600 bacterial species have been detected in the periodontal plaque, the type of bacteria incriminated in the development of the inflammation is still unclear. Moreover, in the last decade gene polymorphisms have been largely recognised as important conditions associated with increased susceptibility to periodontal diseases. Manipulating the immune response by the development of drugs that inhibit adverse host reactions and promote beneficial effects might be of therapeutic or prophylactic importance. This work intends to assess the importance of Toll-like receptors as main effectors of the innate immune response in the triggering, maintenance and progression of periodontal inflammation, as well as of the involvement of synthetic molecules targeting TLR signalling pathways in treating periodontal diseases.

scholarly journals Rab8a localisation and activation by Toll-like receptors on macrophage macropinosomes

2018 ◽  
Vol 374 (1765) ◽  
pp. 20180151 ◽  
Author(s):  
Adam A. Wall ◽  
Nicholas D. Condon ◽  
Lin Luo ◽  
Jennifer L. Stow
Keyword(s):  
Immune Cell ◽  
Light Sheet ◽  
Innate Immune ◽  
Live Cells ◽  
Toll Like Receptors ◽  
Membrane Turnover ◽  
Cell Functions ◽  
Microbial Responses ◽  
Pathogen Entry ◽  
Tlr Signalling

Macropinocytosis is a prevalent and essential pathway in macrophages where it contributes to anti-microbial responses and innate immune cell functions. Cell surface ruffles give rise to phagosomes and to macropinosomes as multi-functional compartments that contribute to environmental sampling, pathogen entry, plasma membrane turnover and receptor signalling. Rapid, high resolution, lattice light sheet imaging demonstrates the dynamic nature of macrophage ruffling. Pathogen-mediated activation of surface and endosomal Toll-like receptors (TLRs) in macrophages upregulates macropinocytosis. Here, using multiple forms of imaging and microscopy, we track membrane-associated, fluorescently-tagged Rab8a expressed in live macrophages, using a variety of cell markers to demonstrate Rab8a localization and its enrichment on early macropinosomes. Production of a novel biosensor and its use for quantitative FRET analysis in live cells, pinpoints macropinosomes as the site for TLR-induced activation of Rab8a. We have previously shown that TLR signalling, cytokine outputs and macrophage programming are regulated by the GTPase Rab8a with PI3 Kγ as its effector. Finally, we highlight another effector, the phosphatase OCRL, which is located on macropinosomes and interacts with Rab8a, suggesting that Rab8a may operate on multiple levels to modulate phosphoinositides in macropinosomes. These findings extend our understanding of macropinosomes as regulatory compartments for innate immune function in macrophages. This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.

TLR4 signalling in the intestine in health and disease

2007 ◽  
Vol 35 (6) ◽  
pp. 1473-1478 ◽  
Author(s):  
M. Fukata ◽  
M.T. Abreu
Keyword(s):  
Mammalian Cells ◽  
Metabolic Energy ◽  
Short Term ◽  
Receptor Signalling ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Term Benefit ◽  
Tlr Signalling

The colonic epithelium is lined along its apical membrane with ∼1014 bacteria/g of tissue. Commensal bacteria outnumber mammalian cells in the gut severalfold. The reason for this degree of commensalism probably resides in the recent recognition of the microbiome as an important source of metabolic energy in the setting of poorly digestible nutrients. As in many themes in biology, the host may have sacrificed short-term benefit, i.e. nutritional advantages, for long-term consequences, such as chronic inflammation or colon cancer. In the present review, we examine the role of TLR (Toll-like receptor) signalling in the healthy host and the diseased host. We pay particular attention to the role of TLR signalling in idiopathic IBD (inflammatory bowel disease) and colitis-associated carcinogenesis. In general, TLR signalling in health contributes to homoeostatic functions. These include induction of antimicrobial peptides, proliferation and wound healing in the intestine. The pathogenesis of IBD, ulcerative colitis and Crohn's disease may be due to increased TLR or decreased TLR signalling respectively. Finally, we discuss the possible role of TLR signalling in colitis-associated neoplasia.

129 The CHR9P21 risk locus affects IL-1/TLR signalling in VSMC

2018 ◽  
Author(s):  
Gemma Basatemur ◽  
Matthew Ackers-Johnson ◽  
Josca Schoonejans ◽  
Anastasiya Kazachenka ◽  
Brian Lam ◽  
...  
Keyword(s):  
Risk Locus ◽  
Tlr Signalling

scholarly journals Melatonin as an immunomodulator in children with Down syndrome

2021 ◽  
Author(s):  
Dean Huggard ◽  
Lynne Kelly ◽  
Amy Worrall ◽  
Eleanor Gallagher ◽  
Lida Fallah ◽  
...  
Keyword(s):  
Immune Response ◽  
Down Syndrome ◽  
Inflammatory Cytokines ◽  
Enzyme Linked Immunosorbent Assay ◽  
List Type ◽  
Tlr4 Expression ◽  
Immunomodulatory Effects ◽  
Children With Down Syndrome ◽  
Anti Inflammatory ◽  
Tlr Signalling

Abstract Background Down syndrome (DS) is a disorder characterised by marked immune dysfunction, increased mortality from sepsis, chronic inflammation, increased oxidative stress, sleep disturbance and possibly abnormal endogenous melatonin levels. Melatonin has a myriad of immune functions, and we hypothesised that this therapeutic agent could modulate the innate immune system in this cohort. Methods We investigated neutrophil and monocyte function (CD11b, TLR4 expression by flow cytometry), genes involved in TLR signalling (MyD88, IRAK4, TRIF), the inflammasome (NLRP3, IL-1β), and circadian rhythm (BMAL, CLOCK, CRY) by qPCR, and inflammatory cytokines (IL-2, IL-6, IL-8, IL-18, IL-1β, TNF-α, IFN-γ, IL-10, IL-1ra, VEGF, Epo, GM-CSF) by enzyme-linked immunosorbent assay (ELISA) following immunomodulation with LPS endotoxin and melatonin. 47 children with DS and 23 age- and sex-matched controls were recruited. Results We demonstrated that melatonin has several significant effects by reducing CD11b and TLR4 expression, attenuating TLR signalling, genes involved in the inflammasome and has the potential to reduce LPS-induced inflammatory responses. Conclusions Immunomodulatory effects of melatonin were found in both paediatric cohorts with more marked effects in the children with DS. Melatonin mediates immune response through a wide array of mechanisms and this immunomodulator may buffer the inflammatory response by regulating pro and anti-inflammatory signalling. Impact We highlight that melatonin mediates its immune response through a wide array of mechanisms, its effects appear to be dose dependant and children with Down syndrome may be more receptive to treatment with it. Immunomodulatory effects of melatonin were demonstrated with marked effects in the children with Down syndrome with a reduction of MyD88, IL-1ß and NLRP3 expression in whole-blood samples. Melatonin is a proposed anti-inflammatory agent with a well-established safety profile, that has the potential for mitigation of pro- and anti-inflammatory cytokines in paediatric Down syndrome cohorts, though further clinical trials are warranted.

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