Oxidation-Specific Epitopes Are Danger-Associated Molecular Patterns Recognized by Pattern Recognition Receptors of Innate Immunity

Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced disruption of TLR4:Siglec E/F interactions. Absence of Neu1 in hematopoietic cells or systematic treatment with sialidase inhibitor Neu5Gc2en protected mice against endotoxemia. Our data raised an intriguing possibility of a broad repression of TLR function by Siglecs and a sialidase-mediated de-repression that allows positive feedback of TLR activation during infection.

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Plant pattern-recognition receptors controlling innate immunity

Science China Life Sciences ◽

10.1007/s11427-016-0115-2 ◽

2016 ◽

Vol 59 (9) ◽

pp. 878-888 ◽

Cited By ~ 22

Author(s):

Lei Li ◽

Yufei Yu ◽

Zhaoyang Zhou ◽

Jian-Min Zhou

Keyword(s):

Pattern Recognition ◽

Innate Immunity ◽

Pattern Recognition Receptors

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Innate immunity — cross-talk with adaptive immunity through pattern recognition receptors and cytokines

Current Opinion in Immunology ◽

10.1016/j.coi.2006.11.018 ◽

2007 ◽

Vol 19 (1) ◽

pp. 1-3 ◽

Cited By ~ 111

Author(s):

Dieter Kabelitz ◽

Ruslan Medzhitov

Keyword(s):

Pattern Recognition ◽

Innate Immunity ◽

Adaptive Immunity ◽

Cross Talk ◽

Pattern Recognition Receptors

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Expression, purification, crystallization and preliminary X-ray analysis of full-length human RIG-I

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x14000430 ◽

2014 ◽

Vol 70 (2) ◽

pp. 248-251

Author(s):

Jane Kwok ◽

Kenrie P. Y. Hui ◽

Julien Lescar ◽

Masayo Kotaka

Keyword(s):

Pattern Recognition ◽

Ebola Virus ◽

Pattern Recognition Receptors ◽

Full Length ◽

Viral Rna ◽

Microbial Pathogens ◽

Diffusion Method ◽

X Ray ◽

Cell Parameters ◽

Molecular Patterns

The human innate immune system can detect invasion by microbial pathogens through pattern-recognition receptors that recognize structurally conserved pathogen-associated molecular patterns. Retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) are one of the two major families of pattern-recognition receptors that can detect viral RNA. RIG-I, belonging to the RLH family, is capable of recognizing intracellular viral RNA from RNA viruses, including influenza virus and Ebola virus. Here, full-length human RIG-I (hRIG-I) was cloned inEscherichia coliand expressed in a recombinant form with a His-SUMO tag. The protein was purified and crystallized at 291 K using the hanging-drop vapour-diffusion method. X-ray diffraction data were collected to 2.85 Å resolution; the crystal belonged to space groupF23, with unit-cell parametersa = b=c= 216.43 Å, α = β = γ = 90°.

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NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase

Journal of Virology ◽

10.1128/jvi.03230-15 ◽

2016 ◽

Vol 90 (13) ◽

pp. 6022-6035 ◽

Cited By ~ 19

Author(s):

Serena Vegna ◽

Damien Gregoire ◽

Marie Moreau ◽

Patrice Lassus ◽

David Durantel ◽

...

Keyword(s):

Pattern Recognition ◽

Innate Immunity ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Inflammatory Response ◽

Cellular Response ◽

Pattern Recognition Receptors ◽

Type I ◽

Mitochondrial Antiviral Signaling

ABSTRACTHepatitis C virus (HCV) triggers innate immunity signaling in the infected cell. Replication of the viral genome is dispensable for this phenotype, and we along with others have recently shown that NS5B, the viral RNA-dependent RNA polymerase, synthesizes double-stranded RNA (dsRNA) from cellular templates, thus eliciting an inflammatory response, notably via activation of type I interferon and lymphotoxin β. Here, we investigated intracellular signal transduction pathways involved in this process. Using HepaRG cells, a model that largely recapitulates thein vivocomplexities of the innate immunity receptor signaling, we have confirmed that NS5B triggered increased expression of the canonical pattern recognition receptors (PRRs) specific for dsRNA, namely, RIG-I, MDA5, and Toll-like receptor 3 (TLR3). Unexpectedly, intracellular dsRNA also led to accumulation of NOD1, a receptor classically involved in recognition of bacterial peptidoglycans. NOD1 activation, confirmed by analysis of its downstream targets, was likely due to its interaction with dsRNA and was independent of RIG-I and mitochondrial antiviral signaling protein (MAVS/IPS-1/Cardif/VISA) signaling. It is likely to have a functional significance in the cellular response in the context of HCV infection since interference with the NOD1 pathway severely reduced the inflammatory response elicited by NS5B.IMPORTANCEIn this study, we show that NOD1, a PRR that normally senses bacterial peptidoglycans, is activated by HCV viral polymerase, probably through an interaction with dsRNA, suggesting that NOD1 acts as an RNA ligand recognition receptor. In consequence, interference with NOD1-mediated signaling significantly weakens the inflammatory response to dsRNA. These results add a new level of complexity to the understanding of the cross talk between different classes of pattern recognition receptors and may be related to certain complications of chronic hepatitis C virus infection.

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PRRDB 2.0: a comprehensive database of pattern-recognition receptors and their ligands

Database ◽

10.1093/database/baz076 ◽

2019 ◽

Vol 2019 ◽

Cited By ~ 6

Author(s):

Dilraj Kaur ◽

Sumeet Patiyal ◽

Neelam Sharma ◽

Salman Sadullah Usmani ◽

Gajendra P S Raghava

Keyword(s):

Pattern Recognition ◽

Data Bank ◽

Pattern Recognition Receptors ◽

Research Articles ◽

Web Based ◽

Source Type ◽

Comprehensive Information ◽

Extensive Information ◽

Function Relationship ◽

Molecular Patterns

Abstract PRRDB 2.0 is an updated version of PRRDB that maintains comprehensive information about pattern-recognition receptors (PRRs) and their ligands. The current version of the database has ~2700 entries, which are nearly five times of the previous version. It contains extensive information about 467 unique PRRs and 827 pathogens-associated molecular patterns (PAMPs), manually extracted from ~600 research articles. It possesses information about PRRs and PAMPs that has been extracted manually from research articles and public databases. Each entry provides comprehensive details about PRRs and PAMPs that includes their name, sequence, origin, source, type, etc. We have provided internal and external links to various databases/resources (like Swiss-Prot, PubChem) to obtain further information about PRRs and their ligands. This database also provides links to ~4500 experimentally determined structures in the protein data bank of various PRRs and their complexes. In addition, 110 PRRs with unknown structures have also been predicted, which are important in order to understand the structure–function relationship between receptors and their ligands. Numerous web-based tools have been integrated into PRRDB 2.0 to facilitate users to perform different tasks like (i) extensive searching of the database; (ii) browsing or categorization of data based on receptors, ligands, source, etc. and (iii) similarity search using BLAST and Smith–Waterman algorithm.

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