Therapeutic Interventions Targeting Innate Immune Receptors: A Balancing Act

2021 ◽  
Author(s):  
Xujun Cao ◽  
Anthony F. Cordova ◽  
Lingyin Li
Keyword(s):  
Innate Immune ◽  
Therapeutic Interventions ◽  
Immune Receptors

scholarly journals Effects of innate immune receptor stimulation on extracellular α-synuclein uptake and degradation by brain resident cells

2021 ◽  
Author(s):  
Changyoun Kim ◽  
Somin Kwon ◽  
Michiyo Iba ◽  
Brian Spencer ◽  
Edward Rockenstein ◽  
...  
Keyword(s):  
Degradation Kinetics ◽  
Morphological Changes ◽  
Direct Interaction ◽  
Innate Immune ◽  
Pathological Feature ◽  
Tlr2 Expression ◽  
Immune Receptors ◽  
Age Related ◽  
Stimulation Of

AbstractSynucleinopathies are age-related neurological disorders characterized by the progressive deposition of α-synuclein (α-syn) aggregates and include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Although cell-to-cell α-syn transmission is thought to play a key role in the spread of α-syn pathology, the detailed mechanism is still unknown. Neuroinflammation is another key pathological feature of synucleinopathies. Previous studies have identified several immune receptors that mediate neuroinflammation in synucleinopathies, such as Toll-like receptor 2 (TLR2). However, the species of α-syn aggregates varies from study to study, and how different α-syn aggregate species interact with innate immune receptors has yet to be addressed. Therefore, we investigated whether innate immune receptors can facilitate the uptake of different species of α-syn aggregates. Here, we examined whether stimulation of TLRs could modulate the cellular uptake and degradation of α-syn fibrils despite a lack of direct interaction. We observed that stimulation of TLR2 in vitro accelerated α-syn fibril uptake in neurons and glia while delaying the degradation of α-syn in neurons and astrocytes. Internalized α-syn was rapidly degraded in microglia regardless of whether TLR2 was stimulated. However, cellular α-syn uptake and degradation kinetics were not altered by TLR4 stimulation. In addition, upregulation of TLR2 expression in a synucleinopathy mouse model increased the density of Lewy-body-like inclusions and induced morphological changes in microglia. Together, these results suggest that cell type-specific modulation of TLR2 may be a multifaceted and promising therapeutic strategy for synucleinopathies; inhibition of neuronal and astroglial TLR2 decreases pathogenic α-syn transmission, but activation of microglial TLR2 enhances microglial extracellular α-syn clearance.

Dysregulation of innate immune receptors on neutrophils in chronic granulomatous disease

2008 ◽  
Vol 121 (2) ◽  
pp. 375-382.e9 ◽  
Author(s):  
Dominik Hartl ◽  
Natalie Lehmann ◽  
Florian Hoffmann ◽  
Annette Jansson ◽  
Andreas Hector ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
Innate Immune ◽  
Granulomatous Disease ◽  
Immune Receptors

Update on the role of innate immune receptors during Brucella abortus infection

2012 ◽  
Vol 148 (1-2) ◽  
pp. 129-135 ◽  
Author(s):  
Sérgio C. Oliveira ◽  
Leonardo A. de Almeida ◽  
Natalia B. Carvalho ◽  
Fernanda S. Oliveira ◽  
Thaís L.S. Lacerda
Keyword(s):  
Brucella Abortus ◽  
Innate Immune ◽  
Immune Receptors

scholarly journals Detection of A-to-I RNA Editing in SARS-COV-2

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 41
Author(s):  
Ernesto Picardi ◽  
Luigi Mansi ◽  
Graziano Pesole
Keyword(s):  
Rna Editing ◽  
Time Course ◽  
Vero Cells ◽  
Innate Immune ◽  
Therapeutic Interventions ◽  
Clinical Samples ◽  
Transcriptome Data ◽  
Host Interactions ◽  
Rnaseq Data ◽  
The Impact

ADAR1-mediated deamination of adenosines in long double-stranded RNAs plays an important role in modulating the innate immune response. However, recent investigations based on metatranscriptomic samples of COVID-19 patients and SARS-COV-2-infected Vero cells have recovered contrasting findings. Using RNAseq data from time course experiments of infected human cell lines and transcriptome data from Vero cells and clinical samples, we prove that A-to-G changes observed in SARS-COV-2 genomes represent genuine RNA editing events, likely mediated by ADAR1. While the A-to-I editing rate is generally low, changes are distributed along the entire viral genome, are overrepresented in exonic regions, and are (in the majority of cases) nonsynonymous. The impact of RNA editing on virus–host interactions could be relevant to identify potential targets for therapeutic interventions.

scholarly journals Therapeutic Interventions into Innate Immune Diseases by Means of Aptamers

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 955
Author(s):  
Farzana Yasmeen ◽  
Hana Seo ◽  
Nasir Javaid ◽  
Moon Suk Kim ◽  
Sangdun Choi
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Crucial Role ◽  
Innate Immune System ◽  
Innate Immune ◽  
Therapeutic Interventions ◽  
Immune System Diseases ◽  
Target Molecules ◽  
Molecular Patterns ◽  
Recognition Receptor

The immune system plays a crucial role in the body’s defense system against various pathogens, such as bacteria, viruses, and parasites, as well as recognizes non-self- and self-molecules. The innate immune system is composed of special receptors known as pattern recognition receptors, which play a crucial role in the identification of pathogen-associated molecular patterns from diverse microorganisms. Any disequilibrium in the activation of a particular pattern recognition receptor leads to various inflammatory, autoimmune, or immunodeficiency diseases. Aptamers are short single-stranded deoxyribonucleic acid or ribonucleic acid molecules, also termed “chemical antibodies,” which have tremendous specificity and affinity for their target molecules. Their features, such as stability, low immunogenicity, ease of manufacturing, and facile screening against a target, make them preferable as therapeutics. Immune-system–targeting aptamers have a great potential as a targeted therapeutic strategy against immune diseases. This review summarizes components of the innate immune system, aptamer production, pharmacokinetic characteristics of aptamers, and aptamers related to innate-immune-system diseases.

scholarly journals Intracellular innate immune receptors: Life inside the cell

2020 ◽  
Vol 297 (1) ◽  
pp. 5-12
Author(s):  
Thirumala‐Devi Kanneganti
Keyword(s):  
Innate Immune ◽  
Immune Receptors

scholarly journals Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells

2020 ◽  
Vol 21 (18) ◽  
pp. 6456
Author(s):  
Yu Fukuda ◽  
Kazuki Nakajima ◽  
Tatsuro Mutoh
Keyword(s):  
Pc12 Cells ◽  
Buoyant Density ◽  
Sucrose Density Gradient ◽  
Subcellular Fractionation ◽  
Innate Immune ◽  
Membrane Microdomains ◽  
Immune Receptors ◽  
Neurite Retraction ◽  
Ischemic Attack ◽  
Molecular Patterns

Infected or damaged tissues release multiple “alert” molecules such as alarmins and damage-associated molecular patterns (DAMPs) that are recognized by innate immune receptors, and induce tissue inflammation, regeneration, and repair. Recently, an extract from inflamed rabbit skin inoculated with vaccinia virus (Neurotropin®, NTP) was found to induce infarct tolerance in mice receiving permanent ischemic attack to the middle cerebral artery. Likewise, we report herein that NTP prevented the neurite retraction in PC12 cells by nerve growth factor (NGF) deprivation. This effect was accompanied by interaction of Fyn with high-affinity NGF receptor TrkA. Sucrose density gradient subcellular fractionation of NTP-treated cells showed heretofore unidentified membrane fractions with a high-buoyant density containing Trk, B subunit of cholera toxin-bound ganglioside, flotillin-1 and Fyn. Additionally, these new membrane fractions also contained Toll-like receptor 4 (TLR4). Inhibition of TLR4 function by TAK-242 prevented the formation of these unidentified membrane fractions and suppressed neuroprotection by NTP. These observations indicate that NTP controls TrkA-mediated signaling through the formation of clusters of new membrane microdomains, thus providing a platform for crosstalk between neurotrophic and innate immune receptors. Neuroprotective mechanisms through the interaction with innate immune systems may provide novel mechanism for neuroprotection.

Sign in / Sign up

Export Citation Format

Share Document