CgIκB3, the third novel inhibitor of NF-kappa B (IκB) protein, is involved in the immune defense of the Pacific oyster, Crassostrea gigas

Xu, Fengjiao; Li, Jun; Zhang, Yuehuan; Li, Xiaomei; Zhang, Yang; Xiang, Zhiming; Yu, Ziniu

doi:10.1016/j.fsi.2015.08.002

Cited by 14 publications

(11 citation statements)

References 36 publications

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“…As a result, three CgIκBs were rigorously modulated during challenge ( Fig. 1b–d ) with different expression pattern, which was similar with previous findings 25 26 , demonstrating the dynamic involvement of NF-κB pathway in immune response of mollusk as well as the functional distinctions among CgIκBs 30 . Moreover, an opposite alternation pattern was observed between the CgIκB2 transcripts and haemocyte phagocytosis ( Fig.…”

Section: Discussionsupporting

confidence: 88%

“…Recently, report in Apostichopus japonicus has also depicted the participation of miRNAs in haemocytes phagocytosis 12 . Given that CgIκBs could repress NF-κB activation in vitro 25 26 , the interaction between cgi-miR-2d and CgIκB2 was therefore supposed to augment haemocyte phagocytosis by modulating NF-κB pathway. Unexpectedly, a significant increase of phagocytic rate was observed in cgi-miR-2d overexpression group ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…A robust immune response to fast eliminate invaded bacteria is therefore greatly needed 20 21 22 . With the release of genome information, oysters have been gradually regarded as a model in investigating invertebrate immune system with some components of NF-κB pathway characterized in the past decades, including one Rel and three IκBs 23 24 25 26 . Meanwhile, more than fifty immune-responsive miRNAs have been identified in C. gigas , among which cgi-miR-2d ( Supplementary Fig.…”

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confidence: 99%

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An invertebrate-specific and immune-responsive microRNA augments oyster haemocyte phagocytosis by targeting CgIκB2

Chen

Zhou

Wang

et al. 2016

Sci Rep

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Nuclear factor (NF)-κB pathway is an evolutionally conserved pathway in activating immune response, in which IκBs can repress the activation. In the present study, cgi-miR-2d, an invertebrate-specific microRNA, was proved to regulate CgIκB2 expression and haemocyte phagocytosis during bacterial infection in oyster Crassostrea gigas. The expression of cgi-miR-2d was significantly up-regulated after Vibrio splendidus challenge, while CgIκB2 transcripts decreased. Significant decreases in both luminescence and CgIκB2 3′UTR level was observed after transfection of cgi-miR-2d in CgIκB2 3′UTR luciferase reporter assay. CgIκB2 mRNA level decreased significantly (0.51-fold of control group, p < 0.05) in gain-of-function assay of cgi-miR-2d in vivo while it increased markedly (1.27-fold, p < 0.05) when cgi-miR-2d was repressed (0.10-fold, p < 0.01). A significant increase of haemocyte phagocytosis rate was observed in cgi-miR-2d overexpression group (p < 0.01), consistent with results in CgIκB2 knock-down group (p < 0.01). Moreover, the apoptosis rate of haemocytes was found significantly declined (28.57%, p < 0.01) in gain-of-function assay of cgi-miR-2d. Together, those results not only depicted the functional conservation of miR-2d family in anti-apoptosis of oysters but also highlighted its interaction with phagocytosis by modulating NF-κB pathway, which might dedicate critically to the well-balance of host immune response.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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An invertebrate-specific and immune-responsive microRNA augments oyster haemocyte phagocytosis by targeting CgIκB2

Chen

Zhou

Wang

et al. 2016

Sci Rep

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“…Moreover, IKK-like and TBK1 genes have been identified in the Pacific oyster (37, 38), as well as a NEMO gene (39). To date, three IκB genes have also been identified in oyster (40, 41). However, the functions of oyster IKK genes involved in innate immune signaling should be further investigated in greater detail.…”

Section: Introductionmentioning

confidence: 99%

Oyster Versatile IKKα/βs Are Involved in Toll-Like Receptor and RIG-I-Like Receptor Signaling for Innate Immune Response

Huang

Zhang

et al. 2019

Front. Immunol.

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IκB kinases (IKKs) play critical roles in innate immunity through signal-induced activation of the key transcription factors nuclear factor-κB (NF-κB) and interferon regulatory factors (IRFs). However, studies of invertebrate IKK functions remain scarce. In this study, we performed phylogenetic analysis of IKKs and IKK-related kinases encoded in the Pacific oyster genome. We then cloned and characterized the oyster IKK α / β -2 gene. We found that oyster IKKα/β-2, a homolog of human IKKα/IKKβ, responded to challenge with lipopolysaccharide (LPS), peptidoglycan (PGN), and polyinosinic-polycytidylic acid [poly(I:C)]. As a versatile immune molecule, IKKα/β-2 activated the promoters of NF- κ B, TNF α, and IFN β, as well as IFN-stimulated response element (ISRE)-containing promoters, initiating an antibacterial or antiviral immune state in mammalian cells. Importantly, together with the cloned oyster IKKα/β-1, we investigated the signal transduction pathways mediated by these two IKKα/β proteins. Our results showed that IKKα/β-1 and IKKα/β-2 could interact with the oyster TNF receptor-associated factor 6 (TRAF6) and that IKKα/β-2 could also bind to the oyster myeloid differentiation factor 88 (MyD88) protein directly, suggesting that oyster IKKα/βs participate in both RIG-I-like receptor (RLR) and Toll-like receptor (TLR) signaling for the reception of upstream immune signals. The fact that IKKα/β-1 and IKKα/β-2 formed homodimers by interacting with themselves and heterodimers by interacting with each other, along with the fact that both oyster IKKα/β proteins interacted with NEMO protein, indicates that oyster IKKα/βs and the scaffold protein NEMO form an IKK complex, which may be a key step in phosphorylating IκB proteins and activating NF-κB. Moreover, we found that oyster IKKα/βs could interact with IRF8, and this may be related to the IKK-mediated activation of ISRE promotors and their involvement in the oyster “interferon (IFN)-like” antiviral pathway. Moreover, the expression of oyster IKKα/β-1 and IKKα/β-2 may induce the phosphorylation of IκB proteins to activate NF-κB. These results reveal the immune function of oyster IKKα/β-2 and establish the existence of mollusk TLR and RLR signaling mediated by IKKα/β proteins for the first time. Our findings should be helpful in deciphering the immune mechanisms of invertebrates and understanding the development of the vertebrate innate immunity network.

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“…Moreover, the presence of two IκB homologs (Cg-IκB1 and Cg-IκB2) and their ability to inhibit NF-κB/Rel transcriptional activity were reported (Montagnani et al, 2008;Zhang et al, 2011). A third Cg-IκB has been recently identified and shown to play a role in host defense by inhibiting persistent over-activation of NF-κB/Rel, especially during the late stage of the immune response (Xu et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Long dsRNAs promote an anti-viral response in Pacific oyster hampering ostreid herpesvirus 1 replication

Pauletto

Segarra

Montagnani

et al. 2017

Journal of Experimental Biology

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Double stranded RNA-mediated genetic interference (RNAi) is a widely used reverse genetic tool for determining the loss-of-function phenotype of a gene. Here, the possible induction of an immune response by long dsRNA was tested in a marine bivalve, i.e. Crassostrea gigas, as well as the specific role of the subunit 2 of the nuclear factor κB inhibitor (IκB2). This gene is a candidate of particular interest for functional investigations in the context of massive mortality oyster events as Cg-IκB2 mRNA levels exhibited significant variation depending on the amount of ostreid herpesvirus 1 (OsHV-1) DNA detected. In the present study, dsRNAs targeting Cg-IκB2 and Green Fluorescence Protein genes were injected in vivo into oysters before being challenged by OsHV-1. Survival appeared close to 100% in both dsRNA injected conditions associated with a low detection of viral DNA and a low expression of a panel of 39 OsHV-1 genes as compared to infected control. Long dsRNA molecules, both Cg-IκB2- and GFP-dsRNA, may have induced an anti-viral state controlling the OsHV-1 replication and precluding the understanding of the Cg-IκB2 specific role. Immune-related genes including Cg-IκB1, Cg-Rel1, Cg-IFI44, Cg-PKR, and Cg-IAP appeared activated in dsRNA-injected condition potentially hampering viral replication and thus conferring a better resistance to OsHV-1 infection. We revealed that long dsRNA-mediated genetic interference triggered an anti-viral state in the oyster, emphasizing the need of new reverse genetics tools for assessing immune gene function and avoiding off-target effects in bivalves

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CgIκB3, the third novel inhibitor of NF-kappa B (IκB) protein, is involved in the immune defense of the Pacific oyster, Crassostrea gigas

Cited by 14 publications

References 36 publications

An invertebrate-specific and immune-responsive microRNA augments oyster haemocyte phagocytosis by targeting CgIκB2

An invertebrate-specific and immune-responsive microRNA augments oyster haemocyte phagocytosis by targeting CgIκB2

Oyster Versatile IKKα/βs Are Involved in Toll-Like Receptor and RIG-I-Like Receptor Signaling for Innate Immune Response

Long dsRNAs promote an anti-viral response in Pacific oyster hampering ostreid herpesvirus 1 replication

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