Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses

Chen, Yujuan; Lin, Junhong; Zhao, Yongkun; Ma, Xianping; Yi, Huashan

doi:10.1631/jzus.b2000808

Cited by 111 publications

(73 citation statements)

References 221 publications

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“…There were also many upregulated genes in the TLRs, such as TLR3, TLR8, and signal mediators (MYD88, IRAK4, IKBKE, and IRAK1). TLR3/MDA5 and TLR8 act as dsRNA and ssRNA sensor, respectively, and upregulation of their expression contributes to the transcriptional activation of IFN-I genes via IRF3/7 phosphorylation (44,45). The upregulation of these genes is similar to results of virus infection studies in Atlantic cod (Gadus morhua) and miiuy croker (Miichthys miiuy) (46, 47).…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of immune parameters, miRNA-mRNA interaction, and immune genes expression in the liver of rainbow trout following infectious hematopoietic necrosis virus infection

Huang

et al. 2022

Front. Immunol.

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Rainbow trout (Oncorhynchus mykiss) is an important economical cold-water fish worldwide. However, infection with infectious hematopoietic necrosis virus (IHNV) has severely restricted the development of aquaculture and caused huge economic losses. Currently, little is known about the immune defense mechanisms of rainbow trout against IHNV. In this study, we detected the changes of immune parameters over different post-infection periods (6-, 12-, 24-, 48-, 72-, 96-, 120-, and 144 hours post-infection (hpi)), mRNA and miRNA expression profiles under 48 hpi (T48L) compared to control (C48L), and key immune-related genes expression patterns in rainbow trout liver following IHNV challenge through biochemical methods, RNA-seq, and qRT-PCR, and the function of miR-330-y was verified by overexpression and silencing in vitro and in vivo. The results revealed that alkaline phosphatase (AKP), alanine aminotransferase (ALT), catalase (CAT), and total superoxide dismutase (T-SOD) activities, and lysozyme (LZM) content showed significant peaks at 48 hpi, whereas malondialdehyde (MDA) content and aspartate aminotransferase (AST) activity decreased continuously during infection, and acid phosphatase (ACP) activity varied slightly. From RNA-seq, a total of 6844 genes and 86 miRNAs were differentially expressed, and numerous immune-related differentially expressed genes (DEGs) involved in RIG-I-like receptor signaling pathway, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, cytokine-cytokine receptor interaction, and antigen processing and presentation were significantly upregulated in T48Lm group, including IFIH1, DHX58, MAVS, TRAF3, IRF3, IRF7, MX1, TLR3, TLR8, MYD88, NOD1, NOD2, IL-8, CXCR1, CD209, CD83, and TAP1. Integrated analysis identified seven miRNAs (miR-425-x, miR-185-x, miR-338-x, miR-330-y, miR-361-x, miR-505-y, and miR-191-x) that target at least three key immune-related DEGs. Expression analysis showed that IFIH1, DHX58, IRF3, IRF7, MX1, TLR3, TLR8, and MYD88 showed a marked increase after 24 hpi during infection. Further research confirmed TAP1 as one of the targets of miR-330-y, overexpression of miR-330-y with mimics or agomir significantly reduced the expression levels of TAP1, IRF3, and IFN, and the opposite effects were obtained by inhibitor. These results facilitate in-depth understanding of the immune mechanisms in rainbow trout against IHNV.

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Section: Discussionmentioning

confidence: 99%

Integrated analysis of immune parameters, miRNA-mRNA interaction, and immune genes expression in the liver of rainbow trout following infectious hematopoietic necrosis virus infection

Huang

et al. 2022

Front. Immunol.

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“…The TLR3 receptor is responsible for recognizing viral dsRNA in cell endosomes. TLR3 activation leads to the production of increased amounts of interferon type I and the death of infected cells [ 19 ]. TLR3 rs5743305 homozygosity may cause malfunction and make cells much more susceptible to viral infections.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the Genes Coding for TLRs, NLRs and RLRs Are Associated with Clinical Parameters of Patients with Acute Myeloid Leukemia

Wicherska‐Pawłowska

Bogunia‐Kubik

Kuszczak

et al. 2022

IJMS

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Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) are major elements of the innate immune system that recognize pathogen-associated molecular patterns. Single-nucleotide polymorphisms (SNPs) in the TLR, NLR, and RLR genes may lead to an imbalance in the production of pro- and anti-inflammatory cytokines, changes in susceptibility to infections, the development of diseases, and carcinogenesis. Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by uncontrolled proliferation of transformed myeloid precursors. We retrospectively analyzed 90 AML patients. We investigated the effect of fifteen SNPs located in the genes coding for RLR1 (rs9695310, rs10738889, rs10813831), NOD1 (rs2075820, rs6958571), NOD2 (rs2066845, rs2066847, rs2066844), TLR3 (rs5743305, rs3775296, 3775291), TLR4 (rs4986791, rs4986790), and TLR9 (rs187084, rs5743836). We observed that TLR4 rs4986791, TLR9 rs5743836, and NOD2 rs2066847 were associated with CRP levels, while RLR-1 rs10738889 was associated with LDH level. Furthermore, we found TLR3 rs5743305 AA to be more common in patients with infections. We also found TLR9 rs187084 C to be associated with more favorable risk, and RLR-1 rs9695310 GG with higher age at diagnosis. In conclusion, the current study showed that SNPs in the genes encoding TLRs, NLRs, and RLRs may be potential biomarkers in patients with AML.

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“…The results suggest that CsTLR7 has a positive role in the clearance of bacterial pathogens ( 65 ). In mammals, TLR3 specifically recognizes viral double-stranded RNA (dsRNA) and triggers toll interleukin-I receptor domain (TIR) through the myeloid differentiation factor 88 (MyD88) non-dependent pathway, activating downstream type I interferon gene expression and the NF-κB signaling pathway to induce an antiviral response in the organism ( 81 ). High expression of TLR3 was detected in the spleen and head kidney of channel catfish infected with virulent Edwardsiella ictalurid ( 82 ).…”

Section: Discussionmentioning

confidence: 99%

Splenic protection network revealed by transcriptome analysis in inactivated vaccine-immunized flounder (Paralichthys olivaceus) against Edwardsiella tarda infection

Xing²,

Tang³

et al. 2022

Front. Immunol.

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The protective immune response produced by fish after vaccination is crucial for vaccine effectiveness. Our previous studies have shown inactivated vaccine against Edwardsiella tarda can induce immune response in flounder (Paralichthys olivaceus). To elucidate the protective immune response at the genetic level, in this study, flounder was immunized with inactivated E. tarda for 5 weeks, and then they were challenged with E. tarda. The spleen was dissected at 7th day post immunization, 1st and 7th day post challenge, respectively. Transcriptome analysis showed that average of 46 million clean reads were obtained per library, while percentage of clean reads being mapped to reference genome was more than 89% in all cases, which suggested good quality of samples. As for differentially expressed genes (DEGs) identification in inactivated E. tarda groups, at 7th day post immunization, 1422 DEGs were identified and significantly enriched in innate immune-related pathways, such as Phagosome, Cell adhesion molecules and NF-kappa B signaling pathway; At 1st post challenge day, 1210 DEGs were identified and enriched to Antigen processing and presentation and Cell adhesion molecules, indicating that the pathogen was rapidly recognized and delivered; At 7th post challenge day, 1929 DEGs were identified, belonged to Toll-like receptor signaling pathway, Antigen processing and presentation, Th1 and Th2 cell differentiation and Th17 cell differentiation. Compared to 7th post immunization day, 73 immune-associated DEGs were identified at 1st post challenge day. Protein-protein interaction networks analysis revealed 11 hub genes (TLR7, TLR3, CXCR4, IFIH1, TLR8 etc), associated with recognition of pathogens and activation of innate immunity; while for 7th post challenge day, 141 immune-associated DEGs were identified. 30 hub genes (IL6, STAT1, HSP90A.1, TLR7, IL12β etc) were associated with stimulation of lymphocyte differentiation and activation of cellular immunity. Ten immune-related genes were randomly selected for RT-qPCR validation at each time point. In conclusion, data revealed protection of flounder against E. tarda infection by inactivated vaccine is mediated via immediate recognition of pathogen and subsequently activation of cellular immunity. Results give new aspect for vaccine protection cascades, is good references for vaccine evaluation.

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Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses

Cited by 111 publications

References 221 publications

Integrated analysis of immune parameters, miRNA-mRNA interaction, and immune genes expression in the liver of rainbow trout following infectious hematopoietic necrosis virus infection

Integrated analysis of immune parameters, miRNA-mRNA interaction, and immune genes expression in the liver of rainbow trout following infectious hematopoietic necrosis virus infection

Polymorphisms in the Genes Coding for TLRs, NLRs and RLRs Are Associated with Clinical Parameters of Patients with Acute Myeloid Leukemia

Splenic protection network revealed by transcriptome analysis in inactivated vaccine-immunized flounder (Paralichthys olivaceus) against Edwardsiella tarda infection

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