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Special Issue "The Role of Toll-Like Receptor Signalling in Sterile Inflammation and Autoimmunity"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 March 2022.

Special Issue Editor

Dr. Kim M. O'sullivan
E-Mail Website
Guest Editor
Centre for Inflammatory Diseases, Monash University, Melbourne, Australia
Interests: TLRs; NETs; autoimmune kidney diseases; ANCA vasculitis; CD4 T cells

Special Issue Information

Dear Colleagues,

Toll-like receptors (TLRs) are key innate pattern recognition receptors (PRRs) which recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPS). TLRs not only play a key role in host defense by recognizing PAMPs on microbes but also provide a strong link between infection, inflammation, and the development of autoimmunity. There is strong evidence that TLRs play a pivotal role in the promotion of inflammation without the presence of infection. TLRs play a non-redundant role in promoting tumor progression and recurrence in cancer, controlling immune responses that maintain gut homeostasis in inflammatory bowel disease, and promoting autoimmune kidney diseases such as Lupus Nephritis and anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). In the context of autoimmunity, self-components released through excessive cell death act as DAMPS, inappropriately activating TLRs. The stimulation of TLRs via their cognate ligands recruits down-stream adaptor molecules. Once these adaptor molecules have been activated, signaling cascades culminate in the activation of transcription factors, such nuclear factor-kB (NFkB) interferons, mitogen-activated protein (MAP) kinases, and response factors (IRFs). These immune response genes induce the production of inflammatory cytokines and inflammation. This Special Issue aims to provide an overview of TLR activation and signaling in the context of non-infectious sterile inflammation and autoimmunity.

Dr. Kim M. O'sullivan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • TLRs
  • PRRs
  • PAMPS
  • signaling adaptor molecules
  • inflammation

Published Papers (2 papers)

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Research

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Article
Induction of Tertiary Phase Epileptiform Discharges after Postasphyxial Infusion of a Toll-Like Receptor 7 Agonist in Preterm Fetal Sheep
Int. J. Mol. Sci. 2021, 22(12), 6593; https://doi.org/10.3390/ijms22126593 - 19 Jun 2021
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Abstract
Background: Toll-like receptor (TLR) agonists are key immunomodulatory factors that can markedly ameliorate or exacerbate hypoxic–ischemic brain injury. We recently demonstrated that central infusion of the TLR7 agonist Gardiquimod (GDQ) following asphyxia was highly neuroprotective after 3 days but not 7 days of [...] Read more.
Background: Toll-like receptor (TLR) agonists are key immunomodulatory factors that can markedly ameliorate or exacerbate hypoxic–ischemic brain injury. We recently demonstrated that central infusion of the TLR7 agonist Gardiquimod (GDQ) following asphyxia was highly neuroprotective after 3 days but not 7 days of recovery. We hypothesize that this apparent transient neuroprotection is associated with modulation of seizure-genic processes and hemodynamic control. Methods: Fetuses received sham asphyxia or asphyxia induced by umbilical cord occlusion (20.9 ± 0.5 min) and were monitored continuously for 7 days. GDQ 3.34 mg or vehicle were infused intracerebroventricularly from 1 to 4 h after asphyxia. Results: GDQ infusion was associated with sustained moderate hypertension that resolved after 72 h recovery. Electrophysiologically, GDQ infusion was associated with reduced number and burden of postasphyxial seizures in the first 18 h of recovery (p < 0.05). Subsequently, GDQ was associated with induction of slow rhythmic epileptiform discharges (EDs) from 72 to 96 h of recovery (p < 0.05 vs asphyxia + vehicle). The total burden of EDs was associated with reduced numbers of neurons in the caudate nucleus (r2 = 0.61, p < 0.05) and CA1/2 hippocampal region (r2 = 0.66, p < 0.05). Conclusion: These data demonstrate that TLR7 activation by GDQ modulated blood pressure and suppressed seizures in the early phase of postasphyxial recovery, with subsequent prolonged induction of epileptiform activity. Speculatively, this may reflect delayed loss of early protection or contribute to differential neuronal survival in subcortical regions. Full article
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Review

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Review
The Role of Toll-like Receptors (TLRs) Mediated Inflammation in Pancreatic Cancer Pathophysiology
Int. J. Mol. Sci. 2021, 22(23), 12743; https://doi.org/10.3390/ijms222312743 - 25 Nov 2021
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Abstract
Pancreatic cancer (PC) is one of the most lethal forms of cancer, characterized by its aggressiveness and metastatic potential. Despite significant improvements in PC treatment and management, the complexity of the molecular pathways underlying its development has severely limited the available therapeutic opportunities. [...] Read more.
Pancreatic cancer (PC) is one of the most lethal forms of cancer, characterized by its aggressiveness and metastatic potential. Despite significant improvements in PC treatment and management, the complexity of the molecular pathways underlying its development has severely limited the available therapeutic opportunities. Toll-like receptors (TLRs) play a pivotal role in inflammation and immune response, as they are involved in pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). Activation of TLRs initiates a signaling cascade, which in turn, leads to the transcription of several genes involved in inflammation and anti-microbial defense. TLRs are also deregulated in several cancers and can be used as prognostic markers and potential targets for cancer-targeted therapy. In this review we discuss the current knowledge about the role of TLRs in PC progression, focusing on the available TLRs-targeting compounds and their possible use in PC therapy. Full article
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