Comparative studies of Toll-like receptor signalling using zebrafish

Kanwal, Zakia; Wiegertjes, G.F.; Veneman, Wouter J.; Meijer, Annemarie H.; Spaink, Herman P.

doi:10.1016/j.dci.2014.02.003

Cited by 79 publications

(54 citation statements)

References 283 publications

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“…Adaptors are recruited. To date, six adaptors of TLRs have been identified in mammals: MyD88, TRIF, TIRAP, TRAM, sterile a and armadillo motif-containing protein 1 (SARM1), and B cell adaptor for phosphoinositide 3-kinase (BCAP), although TRAM is absent in teleost genomes (18,19). In mammals, TLR7/TLR8, TLR9, TLR11, TLR13, and TLR2/ TLR10 recruit MyD88 directly, whereas TLR1, TLR4, TLR5, and TLR6 use TIRAP as the bridging adaptor to recruit MyD88.…”

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confidence: 99%

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Teleost-Specific TLR19 Localizes to Endosome, Recognizes dsRNA, Recruits TRIF, Triggers both IFN and NF-κB Pathways, and Protects Cells from Grass Carp Reovirus Infection

Rao

Wan

et al. 2018

The Journal of Immunology

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TLRs are pivotal pattern recognition receptors in initiating innate immunity and triggering adaptive immunity. TLR pathways have been comprehensively investigated in mammals. However, the teleost-specific TLR19 pathway remains largely unknown. In this study, we identified TLR19 from grass carp (), and explored the ligand, adaptor, and signaling pathways. Pathogen-associated molecular pattern binding and luciferase activity assays indicate that TLR19 recognizes and responds to dsRNA analog (polyinosinic:polycytidylic acid). Confocal fluorescence microscopy demonstrates that TLR19 is synthesized in ribosomes not binding on endoplasmic reticulum, then transfers to early endosome post-polyinosinic:polycytidylic acid stimulation. Fluorescence colocalization and immunoprecipitation experiments confirm TLR19 interacts with adaptor TRIF, not MyD88, TIRAP, or SARM1. TLR19 facilitates protein and phosphorylation levels of IRF3, inhibits phosphorylation of IRF7. TLR19 enhances the promoter activities and mRNA expressions of major IFNs and NF-κBs; in contrast, grass carp TLR3 just significantly motivates IFN1 expression post-grass carp reovirus (GCRV) infection. Further investigations reveal that TLR19 inhibits GCRV replication by overexpression, knockdown, Western blotting techniques and virus titer assays, and protects cells from GCRV infection by flow cytometry and MTT method. Collectively, these results demonstrate that teleost-specific TLR19 recognizes dsRNA, recruits adaptor molecule TRIF, enhances IRF3 protein and phosphorylation levels, triggers both IFN and NF-κB pathways, and prevents viral proliferation. This is the first attempt to systematically clarify the TLR19 signaling pathway, which is the third TLR member recognizing dsRNA. The results will serve the antiviral immune mechanisms in teleost and evolutionary immunology.

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confidence: 99%

“…TLR4 is the only receptor employing TIRAP, MyD88, TRAM, and TRIF. In contrast to these four TLR adaptors, the fifth adaptor, SARM1, and the sixth adaptor, BCAP, are the only adaptor proteins for which a negative role in TLR signaling has been proposed (19).…”

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confidence: 99%

Teleost-Specific TLR19 Localizes to Endosome, Recognizes dsRNA, Recruits TRIF, Triggers both IFN and NF-κB Pathways, and Protects Cells from Grass Carp Reovirus Infection

Rao

Wan

et al. 2018

The Journal of Immunology

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“…Key features of the fish Tlrs and the factors involved in their signalling cascade have high structural similarity to the mammalian Tlr system. The ligand specificity of several Tlr receptors is highly conserved in all vertebrates 35 . Most vertebrate genomes are recognized to have at least one gene representing each of the seven major tlr1 , tlr2 , tlr3 , tlr4 , tlr5 , tlr7 and tlr11 families 36 but the most conserved among zebrafish and human and other mammals models are tlr1 , 2 3 and 9 34 .…”

Section: Discussionmentioning

confidence: 99%

Host-probiotic interaction: new insight into the role of the endocannabinoid system by in vivo and ex vivo approaches

Gioacchini

Rossi

Carnevali

2017

Sci Rep

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The endocannabinoid system plays an important role in regulating inflammation in several chronic or anomalous gut inflammatory diseases. In vivo and ex vivo studies showed that 30 days treatment with a probiotic mix activated the endocannabinoid system in zebrafish. These results highlight the potential of this probiotic mixture to regulate immune cell function, by inducing gene expression of toll-like receptors and other immune related molecules. Furthermore, TUNEL assay showed a decrease in the number of apoptotic cells, and this finding was supported by a reduction in pro-apoptotic factors and an increase in anti-apoptotic molecules. The results presented here strengthen the molecular mechanisms activated by probiotic mix controlling immune response and inflammation.

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“…Toll-like receptors (TLRs) are the best-studied pattern recognition receptors in mammals and play a role in sensing a wide array of pathogen-associated molecular patterns (PAMPs), including peptidoglycan (PGN), lipopolysaccharide (LPS), bacterial DNA, and double-stranded RNA. 1 In addition, TLRs also respond to danger-associated molecular patterns (DAMPs) 2 such as heat-shock proteins, chromatinprotein complexes, oxidized low-density lipoproteins, amyloid-β, and other factors ( Table 1). 3 Toll was first identified in Drosophila and was reported to be involved in the process of fungal infection, which established the immunological function of orthologous TLRs are widely expressed in immune cells.…”

Section: Introductionmentioning

confidence: 99%

Mini-Review: The Non-Immune Functions of Toll-Like Receptors

Song

Shou

et al. 2019

Crit Rev Eukaryot Gene Expr

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Toll-like receptors (TLRs) are a family of highly conserved pattern recognition receptors that can recognize both pathogen-associated molecular patterns and danger-associated molecular patterns. These receptors are important in the activation of the innate immune system and play a role in shaping the adaptive immune system. For years, the expression of TLRs in the brain has been proposed to contribute to the immunological protection of the central nervous system. However, emerging studies have provided increasing evidence of non-immune functions of TLRs and suggest that these receptors may participate in more complex processes that extend beyond the regulation of the innate immune response. In this review, we highlight the expression of TLRs in non-immune cells and epitomize TLR non-immune functions. We aim to reveal the novel roles of TLRs that are distinct from their traditional functions in immunity. Negative regulatory approaches used to study TLR signaling pathways are also discussed, providing potential directions for further studies.

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Comparative studies of Toll-like receptor signalling using zebrafish

Cited by 79 publications

References 283 publications

Teleost-Specific TLR19 Localizes to Endosome, Recognizes dsRNA, Recruits TRIF, Triggers both IFN and NF-κB Pathways, and Protects Cells from Grass Carp Reovirus Infection

Teleost-Specific TLR19 Localizes to Endosome, Recognizes dsRNA, Recruits TRIF, Triggers both IFN and NF-κB Pathways, and Protects Cells from Grass Carp Reovirus Infection

Host-probiotic interaction: new insight into the role of the endocannabinoid system by in vivo and ex vivo approaches

Mini-Review: The Non-Immune Functions of Toll-Like Receptors

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