Functional characterizations of IPS-1 in CIK cells: Potential roles in regulating IFN-I response dependent on IRF7 but not IRF3

Feng, Xiaoli; Zhang, Yixuan; Yang, Chunrong; Liao, Lanjie; Wang, Yaping; Su, Jian

doi:10.1016/j.dci.2015.06.005

Cited by 11 publications

(11 citation statements)

References 38 publications

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“…TLR3 also enhanced mRNA expression of IRF3, not IRF7. However, the RIG-I-like receptor pathway more depends on IRF7, not IRF3 (38,54). The results showed that TLR and RIG-I-like receptor pathways cooperate and have different emphasis on IRF3/7 to defend viral infection.…”

Section: Discussionmentioning

confidence: 93%

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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Section: Discussionmentioning

confidence: 93%

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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“…It has been also shown that fish MAVS is a positive regulator in antiviral immunity . The MAVS is likely to activate IRF3 and IRF7 to trigger the IFN response through the recruitment of signalling molecules, such as TRAF3 and TBK1 (Fig.…”

Section: Signalling Pathways Of Teleost Rlrsmentioning

confidence: 97%

“…Unsurprisingly, MAVS orthologues also exist in teleost fish and have been cloned in several species, including zebrafish, crucian carp, grass carp, black carp, sea perch, large yellow croaker, rock bream ( Oplegnathus fasciatus ), Atlantic salmon, green spotted puffer and Japanese flounder . Teleost MAVS, as an adaptor, seems to have conserved function on the RLR‐mediated signalling pathway, and contains similar protein domains as in mammals, with CARD domain and transmembrane (TM) region at the N‐ and C‐terminuses, respectively (Fig.…”

Section: Signalling Pathways Of Teleost Rlrsmentioning

confidence: 99%

“…Moreover, it was proved that fish IRF3 and IRF7 can activate the IFN promoter via ISRE sites . On the other hand, it was most recently shown that in grass carp, MAVS has its potential role in regulating type I IFN response dependent on IRF7 but not on IRF3, and in zebrafish MAVS variants suppress the induction of type I IFNs by targeting IRF7, implying that fish RLR–MAVS‐mediated signalling pathways may have some functional variations, which are not as exactly observed as in mammals. Hence, it is considered that teleost fish are likely to have conserved RLR signalling pathways; but some detailed signalling regulatory mechanism remains unclear in fish, and IRF3 and IRF7, which function in RLR‐mediated immune responses, need to be further investigated.…”

Section: Signalling Pathways Of Teleost Rlrsmentioning

confidence: 99%

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Retinoic acid‐inducible gene I (RIG‐I)‐like receptors (RLRs) in fish: current knowledge and future perspectives

2017

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Summary Retinoic acid‐inducible gene I (RIG‐I) ‐like receptors (RLRs) are found conservatively present in teleost fish. All three members, RIG‐I, MDA5 and LGP2, together with the downstream molecules such as MITA, TRAF3 and TBK1, have been identified in a range of fish species. However, it is unexpected that RIG‐I has not been reported in fish of Acanthopterygii, and it would be important to clarify the presence and role of the RIG‐I gene in a broad range of taxa in Teleostei. RLRs in fish can be induced in vivo and in vitro by viral pathogens as well as synthetic dsRNA, poly(I:C), leading to the production of type I interferons (IFNs) and the expression of IFN‐stimulated genes (ISGs). Bacterial pathogens, such as Edwardsiella tarda, and their components, such as lipopolysaccharide are also found to induce the expression of RLRs, and whether such induction was mediated through the direct recognition by RLRs or through crosstalk with other pattern recognition receptors recognizing directly bacterial pathogen‐associated molecular patterns awaits to be investigated. On the other hand, RLR‐activated type I IFN production can be negatively regulated in fish by molecules, such as TBK‐1‐like protein and IRF10, which are found to negatively regulate RIG‐I and MAVS‐activated type I IFN production, and to block MITA or bind ISRE motifs, respectively. It is considered that the evolutionary occurrence of RLRs in fish, and their recognized ligands, especially those from their fish pathogens, as well as the mechanisms involved in the RLR signalling pathways, are of significant interest for further investigation.

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“…So far many MAVS orthologs have been detected in teleost fish [ 89 , 91 , 110 , 117 , 118 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 ]. It was observed moreover, that fish MAVS contains similar domains as the mammalian one [ 43 ] and is associated with both RIG-I and MDA5 signaling pathways, and can induce type I IFN response through activation of TRAF3 and TBK1 [ 43 ].…”

Section: Mavsmentioning

confidence: 99%

Cytosolic Sensors for Pathogenic Viral and Bacterial Nucleic Acids in Fish

Mojzesz

Rakus

Chadzińska

et al. 2020

IJMS

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Recognition of the non-self signature of invading pathogens is a crucial step for the initiation of the innate immune mechanisms of the host. The host response to viral and bacterial infection involves sets of pattern recognition receptors (PRRs), which bind evolutionarily conserved pathogen structures, known as pathogen-associated molecular patterns (PAMPs). Recent advances in the identification of different types of PRRs in teleost fish revealed a number of cytosolic sensors for recognition of viral and bacterial nucleic acids. These are DExD/H-box RNA helicases including a group of well-characterized retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) and non-RLR DExD/H-box RNA helicases (e.g., DDX1, DDX3, DHX9, DDX21, DHX36 and DDX41) both involved in recognition of viral RNAs. Another group of PRRs includes cytosolic DNA sensors (CDSs), such as cGAS and LSm14A involved in recognition of viral and intracellular bacterial dsDNAs. Moreover, dsRNA-sensing protein kinase R (PKR), which has a role in antiviral immune responses in higher vertebrates, has been identified in fish. Additionally, fish possess a novel PKR-like protein kinase containing Z-DNA binding domain, known as PKZ. Here, we review the current knowledge concerning cytosolic sensors for recognition of viral and bacterial nucleic acids in teleosts.

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Functional characterizations of IPS-1 in CIK cells: Potential roles in regulating IFN-I response dependent on IRF7 but not IRF3

Cited by 11 publications

References 38 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

Retinoic acid‐inducible gene I (RIG‐I)‐like receptors (RLRs) in fish: current knowledge and future perspectives

Cytosolic Sensors for Pathogenic Viral and Bacterial Nucleic Acids in Fish

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