Akirin2 enhances antibacterial ability via interacting with 14-3-3ζ in V. splendidus-challenged Apostichopus japonicus.

Akirin2 is pivotal for regulating host immunological responses in vertebrates, including antibacterial immunity and inflammation. However, the functional significance of Akirin2 in invertebrates remains largely unexplored. In this study, we cloned the complete cDNA sequence of Akirin2 from A.

Ferroptosis resists intracellular Vibrio splendidus AJ01 mediated by ferroportin in sea cucumber Apostichopus japonicus.

Ferroptosis, a kind of programmed cell death, is characterized with iron-dependent lipid ROS buildup, which is considered as an important cellular immunity in resisting intracellular bacterial infection in mammalian macrophages. In this process, lipid ROS oxidizes the bacterial biofilm to inhibit intracellular bacteria. However, the function of ferroptosis in invertebrate remains unknown.

Identification and functional analysis of Toll-like receptor 2 from razor clam Sinonovacula constricta.

Toll-like receptor 2 (TLR2) is a member of TLR family that plays important roles in the innate immune system, such as pathogen recognition and inflammation regulation. In this study, the TLR2 homologue was cloned from razor clam Sinonovacula constricta (denoted as ScTLR2) and its immune function was explored. The full-length cDNA of ScTLR2 comprised 2890 nucleotides with a 5'-UTR of 218 bp, an open reading frame of 2169 bp encoding 722 amino acids and a 3'-UTR of 503 bp.

A2M possesses anti-bacterial functions by recruiting and enhancing phagocytosis through GRP78 in an echinoderm.

Alpha-2-macroglobulin (A2M) is an extracellular macromolecule mainly known for its role as a broad-spectrum protease inhibitor in mammals. However, the immune recognition and regulation mechanisms of A2M in invertebrates are still not well investigated. In the current study, the role of sea cucumber Apostichopus japonicus A2M in the regulation of innate immune responses was explored.

YTHDC1/CRM1 Facilitates m6A-Modified circRNA388 Nuclear Export to Induce Coelomocyte Autophagy via the miR-2008/ULK Axis in Apostichopus japonicus.

N 6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic RNA, was able to mediate circular RNA (circRNA) function in many immune processes. Nevertheless, the functional role of m6A-modified circRNAs in innate immunity of invertebrates remained unclear. In this study, we identified m6A-modified circRNA388 from cultured sea cucumber (Apostichopus japonicus) coelomocytes, which was mainly detected in cytoplasm after Vibrio splendidus infection.

Dietary Bacillus cereus LS2 protects juvenile sea cucumber Apostichopus japonicus against Vibrio splendidus infection.

This study aimed to investigate the effects of Bacillus cereus LS2 on the growth performance, innate immunity, intestinal microbiota, and disease resistance of sea cucumber Apostichopus japonicus. After feeding with LS2 for 30 days, results showed that dietary with LS2 had a significant improvement in the growth rate and immune parameters (including total coelomocytes counts, phagocytosis, respiratory burst, and immune-related enzymes) of juvenile sea cucumbers. Subsequently, transcriptome sequencing and qRT-PCR verification were performed to analyze the potential mechanism of LS2 diet and thus improve the immune response of A.

Effects of dietary Vibrio sp. 33 on growth, innate immunity, gut microbiota profile and disease resistance against Vibrio splendidus of juvenile sea cucumber Apostichopus japonicus.

To investigate the ability of Vibrio sp. V33 supplementation on the growth performance, innate immunity, intestinal microbiota, and disease resistance of the juvenile sea cucumber Apostichopus japonicus, a feeding experiment was conducted. Our results revealed that dietary Vibrio sp.

NEDD4 activates mitophagy by interacting with LC3 to restrain reactive oxygen species and apoptosis in Apostichopus japonicus challenged with Vibrio splendidus.

Mitophagy, the selective degradation of damaged mitochondria by autophagy, plays a crucial role in the survival of coelomocytes in Apostichopus japonicus following Vibrio splendidus infection by suppressing the generation of reactive oxygen species (ROS) and attenuating cell apoptosis. A recent study revealed that reducing the expression of the neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4), an enzyme 3 (E3) ubiquitin ligase, significantly affects mitochondrial degradation. Prior to the present study, the functional role of NEDD4 in marine invertebrates was largely unexplored.

Nitric oxide synthase regulates coelomocytes apoptosis through the NF-κB signaling pathway in the sea cucumber Apostichopus japonicus.

Nitric oxide synthase (NOS) was initially discovered to participate in the generation of nitric oxide as a defense mechanism against pathogenic infections. In recent years, it has been found that NOS plays a pivotal role in regulating apoptosis and inflammation in mammals. However, the mechanisms underlying NOS-mediated apoptosis in invertebrates remain largely unclear.

Different types of cell death and their shift in shaping disease.

Cell death is the irreversible stop of life. It is also the basic physiological process of all organisms which involved in the embryonic development, organ maintenance and autoimmunity of the body. In recent years, we have gained more comprehension of the mechanism in cell death and have basically clarified the different types of "programmed cell death", such as apoptosis, necroptosis, autophagy, and pyroptosis, and identified some key genes in these processes.

A dataset of micro biodiversity in benthic sediment at a global scale.

Microorganisms, occupying the largest biomass in deep sea, play essential roles in deep-sea ecosystem. It is believed that the microbes in deep-sea sediments are more representative of deep-sea microbial communities, the microbial composition of which is seldom affected by ocean currents. However, the community of benthic microbes on a global scale has not been adequately explored.

Novel secreted STPKLRR from Vibrio splendidus AJ01 promotes pathogen internalization via mediating tropomodulin phosphorylation dependent cytoskeleton rearrangement.

We previously demonstrated that the flagellin of intracellular Vibrio splendidus AJ01 could be specifically identified by tropomodulin (Tmod) and further mediate p53-dependent coelomocyte apoptosis in the sea cucumber Apostichopus japonicus. In higher animals, Tmod serves as a regulator in stabilizing the actin cytoskeleton. However, the mechanism on how AJ01 breaks the AjTmod-stabilized cytoskeleton for internalization remains unclear.

N6-methyladenosine helps Apostichopus japonicus resist Vibrio splendidus infection by targeting coelomocyte autophagy via the AjULK-AjYTHDF/AjEEF-1α axis.

N6-Methyladenosine (m6A) modification is one of the most abundant post-transcriptional modifications that can mediate autophagy in various pathological processes. However, the functional role of m6A in autophagy regulation is not well-documented during Vibrio splendidus infection of Apostichopus japonicus. In this study, the inhibition of m6A level by knockdown of methyltransferase-like 3 (AjMETTL3) significantly decreased V.

METTL3 activates PERK-eIF2α dependent coelomocyte apoptosis by targeting the endoplasmic reticulum degradation-related protein SEL1L in echinoderms.

N6-methyladenosine (m6A) plays an important role in regulating many physiological and disease processes in vertebrates, in which methyltransferase-like 3 (METTL3) is the best-known m6A methyltransferase. However, the functional roles of invertebrate METTL3 have not yet been highlighted. In this study, we found that METTL3 from Apostichopus japonicus (AjMETTL3) was significantly induced in coelomocytes accompanied by higher levels of m6A modification in response to Vibrio splendidus challenge.

Genome-wide identification mA modified circRNAs revealed their key roles in skin ulceration syndrome disease development in Apostichopus japonicus.

Circular RNAs (circRNAs) are novel endogenous non-coding RNAs (ncRNAs) and can be acted as competing endogenous RNAs (ceRNAs) to regulate microRNA (miRNA) and downstream gene expression. Recently, mA modification has been found in circRNA, and mA circRNAs also play important roles in various biological processes and a variety of diseases. Our previous study had been demonstrated that circRNAs were differentially expressed in skin ulceration syndrome (SUS) diseased sea cucumber Apostichopus japonicus.

miR-137 modulates coelomocytes autophagy by targeting Atg13 in the sea cucumber Apostichopus japonicus.

MicroRNAs (miRNAs), as important regulators of host immune responses, play an crucial position in the interaction between host and pathogen by inhibiting the target gene's transcriptional and post-transcriptional expression. A well-validated tumor suppressor, Previously, miR-137 was found to be variably expressed in the sick sea cucumber Apostichopus japonicus specimens by high-throughput sequencing. To further investigate the mechanism of miR-137 regulation of SUS, we identified Atg13 from sea cucumber by dual luciferase reporter assay and RACE (designated as AjAtg13) and was able to serve as a target gene for miR-137.

Vibrio splendidus flagellin C binds tropomodulin to induce p38 MAPK-mediated p53-dependent coelomocyte apoptosis in Echinodermata.

As a typical pathogen-associated molecular pattern, bacterial flagellin can bind Toll-like receptor 5 and the intracellular NAIP5 receptor component of the NLRC4 inflammasome to induce immune responses in mammals. However, these flagellin receptors are generally poorly understood in lower animal species. In this study, we found that the isolated flagellum of Vibrio splendidus AJ01 destroyed the integrity of the tissue structure of coelomocytes and promoted apoptosis in the sea cucumber Apostichopus japonicus.

Global N-methyladenosine methylation analysis reveals the positive correlation between mA modification and mRNA abundance during Apostichopus japonicus disease development.

N-methyladenosine (mA), the most abundant epitranscriptomic modification in eukaryotic messenger RNA (mRNA), plays important roles in regulation of gene expression for fundamental biological processes and diverse physiological functions, including combating with pathogen infection. Here, we were first profile transcriptome-wide mA sequencing in four stages of skin ulceration syndrome-diseased Apostichopus japonicus following Vibrio splendidus infection, including Control (healthy), Early (small ulcer), Later (extensive ulcer), and Resistant (no ulcer) groups. Our results revealed that three experimental groups were all extensively methylated by mA and the proportion of the mA modified genes were also significantly increased to 28.

Dynamic N6-methyladenosine modification of lncRNA modulated by METTL3 during bacterial disease development in an echinoderm.

Long non-coding RNAs (lncRNAs) are novel functional non-coding RNAs which engaged in many aspects of biological processes. N6-methyladenosine (m6A) as a kind of abundant epitranscriptomic modification in eukaryotes, plays important roles in regulation of gene expression for various physiological functions. Our previous study demonstrated that sea cucumber lncRNAs were differentially expressed during bacterial infection.

ROS-mediated BNIP3-dependent mitophagy promotes coelomocyte survival in in response to infection.

Organisms produce high levels of reactive oxygen species (ROS) to kill pathogens or act as signaling molecules to induce immune responses; however, excessive ROS can result in cell death. To maintain ROS balance and cell survival, mitophagy selectively eliminates damaged mitochondria via mitophagy receptors in vertebrates. In marine invertebrates, however, mitophagy and its functions remain largely unknown.

AMPK-mediated glutaminolysis maintains coelomocytes redox homeostasis in Vibrio splendidus-challenged Apostichopus japonicus.

Glutaminolysis has been proved to play an irreplaceable role in vertebrate immunity, including effects on cytokine production, bacterial killing, and redox homeostasis maintenance. Our previous metabolomics analysis indicated that glutaminolysis metabolic substrates glutamine (Gln) and metabolites glutamate (Glu) were significantly lower in Skin ulceration syndrome (SUS)-diseased Apostichopus japonicus. To further delineate the role of glutaminolysis, we assayed the levels of Gln and Glu.

Xenophagy of invasive bacteria is differentially activated and modulated via a TLR-TRAF6-Beclin1 axis in echinoderms.

In marine environments, organisms are confronted with numerous microbial challenges, although the differential regulation of xenophagy in response to different pathogenic bacterial species remains relatively unknown. Here, we addressed this issue using Apostichopus japonicus as a model. We identified 39 conserved autophagy-related genes by genome-wide screening, which provided a molecular basis for autophagy regulation in sea cucumbers.

IL-17/IL-17 Receptor Pathway-Mediated Inflammatory Response in Supports the Conserved Functions of Cytokines in Invertebrates.

Inflammation participates in host defenses against infectious agents and contributes to the pathophysiology of many diseases. IL-17 is a well-known proinflammatory cytokine that contributes to various aspects of inflammation in vertebrates. However, the functional role of invertebrate IL-17 in inflammatory regulation is not well understood.

A unique NLRC4 receptor from echinoderms mediates Vibrio phagocytosis via rearrangement of the cytoskeleton and polymerization of F-actin.

Many members of the nucleotide-binding and oligomerization domain (NACHT)- and leucine-rich-repeat-containing protein (NLR) family play crucial roles in pathogen recognition and innate immune response regulation. In our previous work, a unique and Vibrio splendidus-inducible NLRC4 receptor comprising Ig and NACHT domains was identified from the sea cucumber Apostichopus japonicus, and this receptor lacked the CARD and LRR domains that are typical of common cytoplasmic NLRs. To better understand the functional role of AjNLRC4, we confirmed that AjNLRC4 was a bona fide membrane PRR with two transmembrane structures.

Characterization of Host lncRNAs in Response to Infection and Function as Efficient miRNA Sponges in Sea Cucumber.

Long non-coding RNAs (lncRNAs) have been reported to play critical roles during pathogen infection and innate immune response in mammals. Such observation inspired us to explore the expression profiles and functions of lncRNAs in invertebrates upon bacterial infection. Here, the lncRNAs of sea cucumber () involved in infection were characterized.