Toll-like receptor polymorphisms and susceptibility to human disease

2008 ◽  
Vol 114 (5) ◽  
pp. 347-360 ◽  
Author(s):  
E. Ann Misch ◽  
Thomas R. Hawn
Keyword(s):  
Immune Response ◽  
Disease Susceptibility ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Genetic Studies ◽  
The Past ◽  
Molecular Studies ◽  
Cellular Immune ◽  
Lines Of Evidence

Although several lines of evidence suggest that variation in human inflammation is genetically controlled, the genes which regulate these responses are largely unknown. TLRs (Toll-like receptors) mediate recognition of microbes, regulate activation of the innate immune response and influence the formation of adaptive immunity. Cellular and molecular studies over the past several years have identified a number of common TLR polymorphisms that modify the cellular immune response and production of cytokines in vitro. In addition, human genetic studies suggest that some of these polymorphisms are associated with susceptibility to a spectrum of diseases. In this review, we summarize studies of common TLR polymorphisms and how this work is beginning to illuminate the influence of human variation on inflammation and disease susceptibility.

scholarly journals A Pathogen Mimetic Molecule Induces Highly Amplified Synergistic Immune Activation to Vaccination via Activation of Multiple Signaling Pathways

2020 ◽  
Author(s):  
naorem nihesh ◽  
Saikat Manna ◽  
Bradley Studnitzer ◽  
Jingjing Shen ◽  
Aaron Esser-Kahn
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nlrp3 Inflammasome ◽  
Innate Immune ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Multiple Signaling ◽  
Stimulation Pattern

We developed a small-molecule trimeric PRR agonist-based adjuvant inspired by the stimulation pattern of a pathogen. This molecule generated by covalently linking TLR2/6 agonist, NOD2 agonist, and NLRP3 inflammasome activator, stimulates multiple subfamilies of PRRs in a spatially defined manner resulting in an amplified innate immune response <i>in vitro.</i> Moreover, it elicits both stronger humoral and cellular immune responses <i>in vivo</i>.

scholarly journals A Pathogen Mimetic Molecule Induces Highly Amplified Synergistic Immune Activation to Vaccination via Activation of Multiple Signaling Pathways

2020 ◽  
Author(s):  
naorem nihesh ◽  
Saikat Manna ◽  
Bradley Studnitzer ◽  
Jingjing Shen ◽  
Aaron Esser-Kahn
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nlrp3 Inflammasome ◽  
Innate Immune ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Multiple Signaling ◽  
Stimulation Pattern

We developed a small-molecule trimeric PRR agonist-based adjuvant inspired by the stimulation pattern of a pathogen. This molecule generated by covalently linking TLR2/6 agonist, NOD2 agonist, and NLRP3 inflammasome activator, stimulates multiple subfamilies of PRRs in a spatially defined manner resulting in an amplified innate immune response <i>in vitro.</i> Moreover, it elicits both stronger humoral and cellular immune responses <i>in vivo</i>.

The dysfunctional innate immune response triggered by Toll-like receptor activation is restored by TLR7/TLR8 and TLR9 ligands in cutaneous lichen planus

2014 ◽  
Vol 172 (1) ◽  
pp. 48-55 ◽  
Author(s):  
R. Domingues ◽  
G. Costa de Carvalho ◽  
L.M. da Silva Oliveira ◽  
E. Futata Taniguchi ◽  
J.M. Zimbres ◽  
...  
Keyword(s):  
Immune Response ◽  
Lichen Planus ◽  
Innate Immune Response ◽  
Receptor Activation ◽  
Innate Immune ◽  
Toll Like Receptor

High content screening and computational prediction reveal viral genes that suppress innate immune response

2021 ◽  
Author(s):  
Tai L Ng ◽  
Erika J Olson ◽  
Tae Yeon Yoo ◽  
H. Sloane Weiss ◽  
Yukiye Koide ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Nuclear Transport ◽  
Computational Prediction ◽  
Viral Proteins ◽  
Innate Immune ◽  
Type I ◽  
Viral Genes ◽  
Genes Encoding

Suppression of the host innate immune response is a critical aspect of viral replication. Upon infection, viruses may introduce one or more proteins that inhibit key immune pathways, such as the type I interferon pathway. However, the ability to predict and evaluate viral protein bioactivity on targeted pathways remains challenging and is typically done on a single virus/gene basis. Here, we present a medium-throughput high-content cell-based assay to reveal the immunosuppressive effects of viral proteins. To test the predictive power of our approach, we developed a library of 800 genes encoding known, predicted, and uncharacterized human viral genes. We find that previously known immune suppressors from numerous viral families such as Picornaviridae and Flaviviridae recorded positive responses. These include a number of viral proteases for which we further confirmed that innate immune suppression depends on protease activity. A class of predicted inhibitors encoded by Rhabdoviridae viruses was demonstrated to block nuclear transport, and several previously uncharacterized proteins from uncultivated viruses were shown to inhibit nuclear transport of the transcription factors NF-kB and IRF3. We propose that this pathway-based assay, together with early sequencing, gene synthesis, and viral infection studies, could partly serve as the basis for rapid in vitro characterization of novel viral proteins.

scholarly journals The Hepatitis C Virus-Induced Membranous Web in Liver Tissue

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 191
Author(s):  
Emmanuelle Blanchard ◽  
Philippe Roingeard
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Innate Immune Response ◽  
Liver Tissue ◽  
Hepatoma Cell ◽  
Membrane Vesicles ◽  
Innate Immune ◽  
Host Cell Membrane

Host cell membrane rearrangements induced by the hepatitis C virus (HCV) have been exclusively studied in vitro. These studies have shown that HCV induces double-membrane vesicles (DMVs), which probably serve to separate replication sites from the cytoplasmic sensors of the innate immune response. We report for the first time the observation of HCV-induced membrane rearrangements in liver biopsy specimens from patients chronically infected with HCV. Unlike observations performed in vitro, the membranous web detected in liver tissue seems essentially made of clusters of single-membrane vesicles derived from the endoplasmic reticulum and close to lipid droplets. This suggests that the DMVs could be a hallmark of laboratory-adapted HCV strains, possibly due to their ability to achieve a high level of replication. Alternatively, the concealment of viral RNA in DMVs may be part of innate immune response mechanisms particularly developed in hepatoma cell lines cultured in vitro. In any case, this constitutes the first report showing the differences in the membranous web established by HCV in vitro and in vivo.

scholarly journals In Vitro Analysis of Myd88-mediated Cellular Immune Response to West Nile Virus Mutant Strain Infection

10.3791/52121 ◽  
2014 ◽  
Author(s):  
Guorui Xie ◽  
Melissa C. Whiteman ◽  
Jason A. Wicker ◽  
Alan D.T. Barrett ◽  
Tian Wang
Keyword(s):  
Immune Response ◽  
West Nile Virus ◽  
Mutant Strain ◽  
Cellular Immune Response ◽  
West Nile ◽  
Virus Mutant ◽  
Cellular Immune
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