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Background: Melanoma differentiation-associated gene 5 (MDA5), as a cytoplasmic sensor for viral double-stranded RNAs, has received increasing attention in recent years. Although considerable headway has been made on the functional role of MDA5 in antiviral immunity and autoimmune disease, the available literature is insufficient to assess the vast field. Methods: This study performed a bibliometric analysis to investigate current hotspots in the global scientific output of MDA5 over the past two decades. Related publications and recorded information from 2002 to 2022 in the Web of Science Core Collection (WoSCC) database were retrieved. VOSviewer and CiteSpace were used for quantitative evaluation and visualization. Results: A total of 2267 original articles and reviews were obtained, and the annual number of publications related to MDA5 was increasing rapidly. China has published the most papers, while the USA was the most influential country with the most citations and the highest H-index. The Chinese Academy of Sciences, the United States Department of Health and Human Services, and the Journal of Virology were the most prolific research affiliation, funding source, and journal, respectively. Fujita T (Kyoto University) was the most productive author with the highest H-index and had close cooperation with Kato H and Yoneyama M. The keywords "RIG-I," "MDA5," "innate immunity," "double-stranded-RNA," and "recognition" had the highest frequency, while "dermatomyositis" as well as "autoantibody" seemed to be the emerging hotspots. Conclusion: This study comprehensively demonstrated the research frontiers of MDA5 and will provide a useful resource for scholars to conduct future decisions. Key Points: We conducted the first in-depth survey of the research frontiers on melanoma differentiation-associated gene 5 (MDA5) over the past two decades via bibliometric analysis. We found that many early breakthroughs have been made in the mechanism of MDA5-mediated antiviral immune responses, and the role of MDA5 in autoimmune and autoinflammatory diseases has raised the recent concern. We identified that the virus infection-associated pathogenesis and effective therapeutic strategy of anti-MDA5 antibody-positive dermatomyositis will remain the hotspots in the future. [ABSTRACT FROM AUTHOR]

Acute‐on‐chronic liver failure (ACLF) is a progressive disease that is associated with rapid worsening of clinical symptoms and high mortality. A multicentre prospective study from China demonstrated that patients with hepatitis B virus‐related ACLF (HBV‐ACLF) exhibited worse clinical characteristics and higher mortality rates compared to non‐HBV‐ACLF patients. Immune dysregulation is closely linked to the potential mechanisms of initiation and progression of ACLF. Innate immune response, which is represented by monocytes/macrophages, is up‐regulated across ACLF development. This suggests that monocytes/macrophages play an essential role in maintaining the immune homeostasis of ACLF. Information that has been published in recent years shows that the immune status and function of monocytes/macrophages vary in ACLF precipitated by different chronic liver diseases. Monocytes/macrophages have an immune activation effect in hepatitis B‐precipitated‐ACLF, but they exhibit an immune suppression in cirrhosis‐precipitated‐ACLF. Therefore, this review aims to explain whether this difference affects the clinical outcome in HBV‐ACLF patients as well as the mechanisms involved. We summarize the novel findings that highlight the dynamic polarization phenotype and functional status of hepatic macrophages from the stage of HBV infection to ACLF development. Moreover, we discuss how different HBV‐related liver disease tissue microenvironments affect the phenotype and function of hepatic macrophages. In summary, increasing developments in understanding the differences in immune phenotype and functional status of hepatic macrophages in ACLF patients will provide new perspectives towards the effective restoration of ACLF immune homeostasis. [ABSTRACT FROM AUTHOR]

Serine protease inhibitors (serpins) appear to be ubiquitous in almost all living organisms, with a conserved structure and varying functions. Serpins can modulate immune responses by negatively regulating serine protease activities strictly and precisely. The codling moth, Cydia pomonella (L.), a major invasive pest in China, can cause serious economic losses. However, knowledge of serpin genes in this insect remain largely unknown. In this study, we performed a systematic analysis of the serpin genes in C. pomonella, obtaining 26 serpins from the C. pomonella genome. Subsequently, their sequence features, evolutionary relationship, and expression pattern were characterized. Comparative analysis revealed the evolution of a number of serpin genes in Lepidoptera. Importantly, the evolutionary relationship and putative roles of serpin genes in C. pomonella were revealed. Additionally, selective pressure analysis found amino acid sites with strong evidence of positive selection. Interestingly, the serpin1 gene possessed at least six splicing isoforms with distinct reactive-center loops, and these isoforms were experimentally validated. Furthermore, we observed a subclade expansion of serpins, and these genes showed high expression in multiple tissues, suggesting their important roles in C. pomonella. Overall, this study will enrich our knowledge of the immunity of C. pomonella and help to elucidate the role of serpins in the immune response. [ABSTRACT FROM AUTHOR]

Coumarin is a natural compound from plants with the molecular formula C 9 H 6 O 2. Cherax quadricarinatus (red claw crayfish) is an aquaculture species exhibiting high economic efficiency and quality that is mainly distributed and cultivated in the southeast provinces in China. In order to identify an effective herbal immunopotentiator against white spot syndrome virus (WSSV) infection, this study examined the effect of coumarin as a feed additive in protecting C. quadricarinatus against WSSV infection. The expression of immune-related genes and WSSV copies were analyzed by Q-PCR. Challenge experiments were conducted to analyze the survival rate and determine the optimal concentration of coumarin. The Phenoloxidase activity (PO), Acid phosphatase (ACP) and superoxide dismutase activity (SOD) activity and lysozyme activity were also analyzed. Total hemocyte count (THC) and apoptosis rate were determined by flow cytometry. The WSSV challenge results showed that 40 mg/kg coumarin reduced the mortality of C. quadricarinatus and delayed the WSSV infection process. Further investigation showed that coumarin treatment had a positive effect on the important immunity-related parameters THC, ACP activity, SOD activity, LZM and PO activity. Coumarin up-regulated the expression of proPO, JAK, STAT, ALF, Hsp70 and down-regulated the expression of caspase at the mRNA level. After WSSV infection, the hemocyte apoptosis rate was lower in the 40 mg/kg coumarin + WSSV group compared with the WSSV only group. These data illustrate that coumarin enhances innate immunity in C. quadricarinatus and exhibits a protective effect against WSSV infection by reducing the number of WSSV copies and slowing the process of infection, which provides a potential theoretical basis for studies of coumarin as a new aquatic feed additive in crustacean aquaculture. • Coumarin could enhance the survival rate of WSSV-infected crayfish. • Coumarin promoted the activities of PO, SOD, and ACP in crayfish. • Coumarin reduced the apoptosis of hemocytes in crayfish. [ABSTRACT FROM AUTHOR]

Grass carp (Ctenopharyngodon idella) is a widely cultivated freshwater fish in the world, which occupies a leading position in China's aquaculture industry. However, the outbreak of hemorrhagic disease resulted from grass carp reovirus (GCRV) infection causes tremendous loss in grass carp production. In this study, we cloned the cDNA of grass carp SIRT3 (gc-SIRT3) and found that it is highly conserved across species and abundantly expressed in grass carp liver. Upon GCRV infection, the expression of gc-SIRT3 is dynamically changed. In addition, grass carp SIRT3 positively regulates the expression of antiviral genes depending on its enzymatic activity. Mechanistically, gc-SIRT3 interacts with gc-MAVS to enhance the MAVS-mediated antiviral response. Furthermore, SIRT3 inhibition in zebrafish or grass carp larvae with the specific inhibitor, 3-TYP, attenuates the antiviral ability against GCRV infection. Our findings may provide clues for understanding the function of SIRT3 in antiviral innate immunity. • Grass carp SIRT3 expression is dynamically changed upon GCRV infection. • Grass carp SIRT3 enhances antiviral gene expression depending on its enzymatic activity. • Grass carp SIRT3 interacts with MAVS to enhance the MAVS-mediated antiviral response. • SIRT3 inhibition with 3-TYP attenuates the antiviral ability against GCRV infection. [ABSTRACT FROM AUTHOR]

In China, Procambarus clarkii has grown to be one of the most important cultivated crustacean species due to its excellent resistance ability against viral and bacterial infection. However, this broad-spectrum mechanism of disease resistance is less well known. In this study, a new LGBP known as Pc LGBP was cloned and described. Its full-length cDNA is 1200 bp with an open reading frame (ORF) of 1086 bp, encoding a 361 amino acid polypeptide. The transcripts of Pc LGBP were widely dispersed in P. clarkii tissues, with particularly elevated expression levels in hemocytes. Furthermore, Aeromonas hydrophila and white spot syndrome virus (WSSV) challenge dramatically increased its mRNA expression in hemocytes and gills. The purified recombinant Pc LGBP protein could bind to different kinds of pathogenic microorganisms, demonstrating a broad-spectrum pathogen recognition ability. Besides, Pc LGBP knockdown by RNA interference and r Pc LGBP injection experiments confirmed that the protein could apparently accelerate the bacterial clearance and inhibit the WSSV proliferation in vivo , thus increase the survival rate of A. hydrophila or WSSV infected P. clarkii. Further studies revealed that silencing of Pc LGBP resulted in inactivation of prophenoloxidase (proPO) system, decreased the expression levels of Toll/IMD pathway components, as well as some antimicrobial peptides (AMPs). Taken together, Pc LGBP may protect P. clarkii from diverse invading pathogens through activating the proPO system, NF-κB pathway and the expression of AMPs. These findings would contribute to the exploration of the crustacean immunity regulatory mechanisms and hold potential for the disease resistance breeding of P. clarkii. • A novel member of LGBP family named Pc LGBP was identified in Procambarus clarkii. • Pc LGBP was involved in both anti-bacterial and anti-viral immune response. • Pc LGBP exhibited broad-spectrum resistance ability in vivo. • Pc LGBP participate in the activation of the proPO system and NF-κB pathway. [ABSTRACT FROM AUTHOR]

New emerging viruses belonging to the Coronaviridae, Flaviviridae, and Filoviridae families are serious threats to public health and represent a global concern. The surveillance to monitor the emergence of new viruses and their transmission is an important target for public health authorities. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an excellent example of a pathogen able to cause a pandemic. In a few months, SARS-CoV-2 has spread globally from China, and it has become a world health problem. Gammadelta (γδ) T cell are sentinels of innate immunity and are able to protect the host from viral infections. They enrich many tissues, such as the skin, intestines, and lungs where they can sense and fight the microbes, thus contributing to the protective immune response. γδ T cells perform their direct antiviral activity by cytolytic and non-cytolytic mechanisms against a wide range of viruses, and they are able to orchestrate the cellular interplay between innate and acquired immunity. For their pleiotropic features, γδ T cells have been proposed as a target for immunotherapies in both cancer and viral infections. In this review, we analyzed the role of γδ T cells in emerging viral infections to define the profile of the response and to better depict their role in the host protection. [ABSTRACT FROM AUTHOR]

Simple Summary: The Asian corn borer, Ostrinia furnacalis (Guenée), is the most destructive lepidopteran insect pest of corn (Zea mays L.) in China. Pathogenic microorganisms play an important role in the population control of the Asian corn borer. Although microorganisms can cause the death of O. furnacalis, an immune response also occurs as an attempt to fight off and eliminate invading pathogens. If the molecular mechanism of interaction between O. furnacalis and pathogenic bacteria is clarified, the lethal effect of pathogenic microorganisms can be better exerted by inhibiting the natural immune response of O. furnacalis. As an important member of the pattern-recognition receptor family, peptidoglycan recognition protein (PGRP) plays a key role in the insect innate immune response. In this study, we cloned two PGRP genes from O. furnacalis and analyzed their spatiotemporal expression. In combination with bacterial induction experiments, we revealed the immune signal recognition pathway involved in the two proteins. The results of this study deepen the understanding of the natural immune response of O. furnacalis and provide new ideas for better utilization of pathogenic microorganisms in biological control of the Asian corn borer. Peptidoglycan recognition proteins (PGRPs) are important components of insect immune systems, in which they play key roles. We cloned and sequenced two full-length PGRP, named OfPGRP-A and OfPGRP-B, from the Asian corn borer, Ostrinia furnacalis. These two genes comprise open reading frames of 658 and 759 bp, encoding proteins of 192 and 218 amino acids, respectively. qPCR showed that OfPGRP-A and OfPGRP-B are prominently expressed in the midgut of O. furnacalis fourth instar larvae. After inoculation with Staphylococcus aureus and Bacillus thuringiensis, the expression of OfPGRP-A was significantly upregulated, whereas the expression of OfPGRP-B was enhanced after inoculation with Escherichia coli. This suggests that OfPGRP-A mainly recognizes Gram-positive bacteria and may participate in the Toll signaling pathways, while OfPGRP-B identifies Gram-negative bacteria and may participate in Imd signaling pathways. Our results provide insights into the roles of PGRPs in O. furnacalis immune function and a foundation for using pathogens for the biological control of O. furnacalis. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death in both China and developed countries due to its high incidence and low cure rate. Immune function is closely linked to the development and progression of tumors. Platelets, which are primarily known for their role in hemostasis, also play a crucial part in the spread and progression of tumors through their interaction with the immune microenvironment. The impact of platelets on tumor growth and metastasis depends on the type of cancer and treatment method used. This article provides an overview of the relationship between platelets and the immune microenvironment, highlighting how platelets can either protect or harm the immune response and cancer immune escape. We also explore the potential of available platelet-targeting strategies for tumor immunotherapy, as well as the promise of new platelet-targeted tumor therapy methods through further research. • Platelets can affect the immune environment by either aiding or hindering the immune response and helping cancer cells evade the immune system. • Possible benefit of anti-platelet agents in cancer patients has been discussed, along with the underlying mechanisms. • The potential of available platelet-targeting strategies for tumor immunotherapy was presented. • Questions have been raised about the role of platelets in the immune needs of tumor cells during cancer development and spread. [ABSTRACT FROM AUTHOR]

The large yellow croaker (Larimichthys crocea) stands as a cornerstone of mariculture in China due to its significant value. However, the threat of Pseudomonas plecoglossicida infection looms large, capable of triggering "visceral white spot disease" and subsequently inflicting severe economic ramifications. Through a prior genome-wide association analysis (GWAS) aimed at understanding the resistance of the large yellow croaker to this ailment, a pivotal player emerged: the complement component 1q binding protein, aptly named LcC1qbp. This protein assumes a crucial role in the activation of the complement system. This study delves deeper into the immune response by examining the expression patterns of LcC1QBP when confronted with P. plecoglossicida. The investigation into gene expression patterns reveals LcC1qbp ′s widespread presence, with its highest transcriptional abundance identified in the kidney tissues. Upon infection by P. plecoglossicida , the up-regulation of LcC1qbp in major immune organs manifests at both the transcriptional and translational levels. In the context of RNA interference, transcriptome analysis of C1qbp in HEK 293T cells uncovers 1327 differentially expressed genes (DEGs), featuring 41 significant immune genes. This includes pivotal components such as C1S and C3 of the complement system, along with IL11 , IL12RB2 , and Myd88 , among others. The outcomes of enrichment analysis spotlight the prevalence of DEGs within key pathways like immune system development, myeloid leukocyte-mediated immunity, MAPK signaling, and other immune-related routes. By unveiling the immune response mechanisms of the large yellow croaker to P. plecoglossicida infection, this study bolsters our understanding. Furthermore, it lays the groundwork for pursuing effective strategies in both preventing and treating "visceral white spot disease" in the large yellow croaker. • LcC1qbp was reported on the role in the immune response of teleost fish for the first time. • LcC1qbp was in cytoplasm and nucleus in Larimichthys crocea head-kidney cells. • The expression of LcC1qbp mRNA was significantly induced after Pseudomonas plecoglossicida stimulation. • C1s, C3, CXCR4, TLRs and Myd88 might play important regulatory roles to C1qbp in fish. • LcC1qbp resists Pseudomonas plecoglossicida stimulation by activating the complement ststem. [ABSTRACT FROM AUTHOR]

At the end of December 2019, the COVID-19 pandemic began in Wuhan of China. COVID-19 affects different people with a wide spectrum of clinical manifestations, ranging from asymptomatic with recovery without hospitalization up to a severe acute respiratory syndrome (SARS). The innate and adaptive immunity appears responsible for the defense against the virus and recovery from the disease. The innate immune system, as the first line of defense, is essential for the detection of virus and subsequent activation of acquired immunity. The innate immune response is carried out by sentinel cells such as monocytes/macrophages and dendritic cells and by receptors known as pattern recognition receptors (PRR). These receptors can recognize various components of the virus, which lead to intracellular signaling and subsequently the synthesis of various cytokines. These cytokines then recruit other immune cells, activate adaptive immune responses, and inhibit viral spreading. The most common receptors include Toll-like receptors, C-type lectin receptors, and RIG-I like receptors. This review describes the current knowledge about the interplay between innate immune responses and SARS-CoV-2 with a focus on the innate immune cells and the role of their receptors in viral RNA recognition, as well as their mechanisms for recognizing SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Wnt2 is a significant factor in the Wnt signaling pathway, which is associated with a variety of physiological activities, including inflammatory response, cell apoptosis, reproductive system development, and cell differentiation. Hyriopsis cumingii is the main pearl breeding mussel in China. However, the role of wnt2 in this species remains unclear. In this study, wnt2 from H. cumingii was cloned and identified. The full-length cDNA of wnt2 is 1524 bp, containing a 963 bp open reading frame (ORF), encoding 320 amino acid residues. The tissue distribution of H. cumingii indicated that wnt2 was predominantly highly expressed in the ovary and gill. And the expression profile after Aeromonas hydrophila or LPS injection indicated that wnt2 was up-regulated in gill, suggesting its role in the innate immune response. The expression of wnt2 was high at 4-month-old of early gonadal development and throughout ovarian development. In situ hybridization (ISH) showed significant hybridization signals on the gills and mature eggs of female gonads. In addition, miR-1988b-5p was found to negatively regulate wnt2 to affect the expression of key genes (frizzled-5 , ctnnb1 , and tcf7l) in the Wnt signaling pathway. Thus, these findings suggest a key role for wnt2 in immune regulation and gonadal development in H. cumingii. • wnt2 of Hyriopsis cumingii was identified and characterized. • The highest wnt2 expression was observed in ovary and gill. • wnt2 is up-regulated in gill following Aeromonas hydrophila /LPS exposure. • wnt2 is involved in immune regulation and gonadal development of H.cumingii. • MiR-1988b-5p affects Wnt signaling pathway genes expression by targeting wnt2. [ABSTRACT FROM AUTHOR]

Background: African swine fever virus (ASFV) is a highly lethal virus that can infect porcine alveolar macrophages (PAMs). Since ASFV, China has dealt with a heavy blow to the pig industry. However, the effect of infection of ASFV strains isolated from China on PAM transcription level is not yet clarified. Methods: In this study, RNA sequencing (RNA-seq) was used to detect the differential expression of genes in PAMs at different time points after ASFV-CN/GS/2018 infection. The fluorescent quantitative polymerase chain reaction (qPCR) method was used to confirm the altered expression of related genes in PAMs infected with ASFV. Results: A total of 1154 differentially expressed genes were identified after ASFV-CN/GS/2018 infection, of which 816 were upregulated, and 338 were downregulated. GO and KEGG analysis showed that these genes were dynamically enriched in various biological processes, including innate immune response, inflammatory response, chemokines, and apoptosis. Furthermore, qPCR verified that the DEAD box polypeptide 58 (DDX58), Interferon-induced helicase C domain-containing protein 1 (IFIH1), Toll-like receptor 3 (TLR3), and TLR7 of PAMs were upregulated after ASFV infection, while TLR4 and TLR6 had a significant downward trend during ASFV infection. The expression of some factors related to antiviral and inflammation was altered significantly after ASFV infection, among which interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), IFIT2, Interleukin-6 (IL-6) were upregulated, and Ewing's tumor-associated antigen 1 homolog (ETAA1) and Prosaposin receptor GPR37 (GPR37) were downregulated. In addition, we discovered that ASFV infection is involved in the regulation of chemokine expression in PAMs, and the chemokines, such as C-X-C motif chemokine 8 (CXCL8) and CXCL10, were upregulated after infection. However, the expression of chemokine receptor C-X-C chemokine receptor type 2 (CXCR2) is downregulated. Also, that the transcriptional levels of pro-apoptotic and anti-apoptotic factors changed after infection. Conclusions: After ASFV-CN/GS/2018 infection, the expression of some antiviral and inflammatory factors in PAMs changed significantly. The ASFV infection may activates the RLR and TLR signaling pathways. In addition, ASFV infection is involved in regulating of chemokine expression in PAMs and host cell apoptosis. [ABSTRACT FROM AUTHOR]

Background: African swine fever virus (ASFV) is a highly lethal virus that can infect porcine alveolar macrophages (PAMs). Since ASFV, China has dealt with a heavy blow to the pig industry. However, the effect of infection of ASFV strains isolated from China on PAM transcription level is not yet clarified. Methods: In this study, RNA sequencing (RNA-seq) was used to detect the differential expression of genes in PAMs at different time points after ASFV-CN/GS/2018 infection. The fluorescent quantitative polymerase chain reaction (qPCR) method was used to confirm the altered expression of related genes in PAMs infected with ASFV. Results: A total of 1154 differentially expressed genes were identified after ASFV-CN/GS/2018 infection, of which 816 were upregulated, and 338 were downregulated. GO and KEGG analysis showed that these genes were dynamically enriched in various biological processes, including innate immune response, inflammatory response, chemokines, and apoptosis. Furthermore, qPCR verified that the DEAD box polypeptide 58 (DDX58), Interferon-induced helicase C domain-containing protein 1 (IFIH1), Toll-like receptor 3 (TLR3), and TLR7 of PAMs were upregulated after ASFV infection, while TLR4 and TLR6 had a significant downward trend during ASFV infection. The expression of some factors related to antiviral and inflammation was altered significantly after ASFV infection, among which interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), IFIT2, Interleukin-6 (IL-6) were upregulated, and Ewing's tumor-associated antigen 1 homolog (ETAA1) and Prosaposin receptor GPR37 (GPR37) were downregulated. In addition, we discovered that ASFV infection is involved in the regulation of chemokine expression in PAMs, and the chemokines, such as C-X-C motif chemokine 8 (CXCL8) and CXCL10, were upregulated after infection. However, the expression of chemokine receptor C-X-C chemokine receptor type 2 (CXCR2) is downregulated. Also, that the transcriptional levels of pro-apoptotic and anti-apoptotic factors changed after infection. Conclusions: After ASFV-CN/GS/2018 infection, the expression of some antiviral and inflammatory factors in PAMs changed significantly. The ASFV infection may activates the RLR and TLR signaling pathways. In addition, ASFV infection is involved in regulating of chemokine expression in PAMs and host cell apoptosis. [ABSTRACT FROM AUTHOR]

C-type lectins (CTL) are a large group of pattern-recognition proteins and to play important roles in glycoprotein metabolism, multicellular integration, and immunity. Based on their overall domain structure, they can be classified as different groups that possess different physiological functions. A typical C-type lectin (named as Om Lec1) was identified from the fish, Onychostoma macrolepis , an important cultured fish in China. Open reading frame of Om Lec1 contains a 570 bp, encoding a protein of 189 amino acids that includes a signal peptide and a single carbohydrate-recognition domain. The phylogenetic analysis showed that Om Lec1 could be grouped with C-type lectin from other fish. Om Lec1 was expressed in all the tissues in our study, and the expression level was highest in liver. And its relative expression levels were significantly upregulated following infection with Aeromonas hydrophila. The recombinant Om Lec1 protein (r Om Lec1) could agglutinate some Gram-negative bacteria and Gram-positive bacteria in vitro in the presence of Ca2+, showing a typical Ca2+-dependent carbohydrate-binding protein. Furthermore, r Om Lec1 purified from E. coli BL21 (DE3), strongly bound to LPS and PGN, as well as all tested bacteria in a Ca2+-dependent manner. These results indicate that Om Lec1 plays a central role in the innate immune response and as a pattern recognition receptor that recognizes diverse pathogens among O. macrolepis. • A typical C-type lectin with a EPN/WND motif (Om Lec1) was identified and characterized from Onychostoma macrolepis. • The expression levels of Om Lec1 gene were significantly up-regulated after pathogen challenge. • Recombinant Om Lec1 can agglutinates various bacteria in vitro in the presence of Ca2+. • Recombinant Om Lec1 could bind some saccharides such as d -mannose, LPS and PGN. [ABSTRACT FROM AUTHOR]

BACKGROUNDDespite an increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the tumor-associated myeloid response balance and its translational value. We aimed to construct a simple and reliable myeloid signature for hepatocellular carcinoma (HCC).METHODSUsing in situ immunohistochemistry, we assessed the distribution of major myeloid subtypes in both peri- and intratumoral regions of HCC. A 2-feature-based, myeloid-specific prognostic signature, named the myeloid response score (MRS), was constructed using an L1-penalized Cox regression model based on data from a training subset (n = 244), a test subset (n = 244), and an independent internal (n = 341) and 2 external (n = 94; n = 254) cohorts.RESULTSThe MRS and the MRS-based nomograms displayed remarkable discriminatory power, accuracy, and clinical usefulness for predicting recurrence and patient survival, superior to current staging algorithms. Moreover, an increase in MRS was associated with a shift in the myeloid response balance from antitumor to protumor activities, accompanied by enhanced CD8+ T cell exhaustion patterns. Additionally, we provide evidence that the MRS was associated with the efficacy of sorafenib treatment for recurrent HCC.CONCLUSIONWe identified and validated a simple myeloid signature for HCC that showed remarkable prognostic potential and may serve as a basis for the stratification of HCC immune subtypes.FUNDINGThis work was supported by the National Science and Technology Major Project of China, the National Natural Science Foundation of China, the Science and Information Technology of Guangzhou, the Fundamental Research Funds for the Central Universities, the Guangdong Basic and Applied Basic Research Foundation, and the China Postdoctoral Science Foundation. [ABSTRACT FROM AUTHOR]

The migratory plant‐parasitic nematode Bursaphelenchus xylophilus is the causal agent of pine wilt disease, which causes serious damage to pine forests in China. Plant immunity plays an important role in plant resistance to multiple pathogens. Activation of the plant immune system is generally determined by immune receptors, including plant pattern recognition receptors, which mediate pattern recognition. However, little is known about molecular pattern recognition in the interaction between pines and B. xylophilus. Based on the B. xylophilus transcriptome at the early stages of infection and Agrobacterium tumefaciens‐mediated transient expression and infiltration of recombinant proteins produced by Pichia pastoris in many plant species, a novel molecular pattern (BxCDP1) was characterized in B. xylophilus. We found that BxCDP1 was highly up‐regulated at the early infection stages of B. xylophilus, and was similar to a protein in Pararhizobium haloflavum. BxCDP1 triggered cell death in Nicotiana benthamiana when secreted into the apoplast, and this effect was dependent on brassinosteroid‐insensitive 1‐associated kinase 1, but independent of suppressor of BIR1‐1. BxCDP1 also exhibited cell death‐inducing activity in pine, Arabidopsis, tomato, pepper, and lettuce. BxCDP1 triggered reactive oxygen species production and the expression of PAMP‐triggered immunity marker genes (NbAcre31, NbPTI5, and NbCyp71D20) in N. benthamiana. It also induced the expression of pathogenesis‐related genes (PtPR‐3, PtPR‐4, and PtPR‐5) in Pinus thunbergii. These results suggest that as a new B. xylophilus molecular pattern, BxCDP1 can not only be recognized by many plant species, but also triggers innate immunity in N. benthamiana and defence responses of P. thunbergii. [ABSTRACT FROM AUTHOR]

Purpose: Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that mediates cellular responses to interferons (IFNs) and other cytokines and growth factors in diverse cell types. STAT1 gain-of-function (GOF) mutations result in an unexpectedly wide range of clinical features. It remains unclear why STAT1 GOF mutations result in such a broad spectrum of phenotypes. Methods: We analyzed the clinical, molecular, and phenotypic characteristics of nine Chinese patients with STAT1 GOF mutations. Results: This study enrolled nine patients with STAT1 GOF mutations including five novel mutations. We discuss the molecular and phenotypic characterization such as unique Penicillium marneffei lymphadenitis. Patients with STAT1 GOF mutations had defects in both innate and adaptive immunity, including impaired T cell receptor (TCR) diversity; reduced numbers of naïve and effector memory CD4+ T cells, memory B cells, and NK cells; and defects in the production of IL-17A and IFN-γ. In addition, experiments with primary immune cells revealed that enhanced STAT1 phosphorylation resulted from not only lower rates of STAT1 dephosphorylation but also increased total STAT1 expression. Conclusions: Our report provides the first comprehensive overview of the molecular genetics, clinical heterogeneity, and underlying immunological abnormalities of patients with STAT1 GOF mutations in China. In further study, to find the relationship between different STAT1 GOF mutations and clinical phenotype as well as the mechanism of increased total STAT1 expression will be needed. [ABSTRACT FROM AUTHOR]

Avian Tembusu virus (TMUV) is a newly emerging avian pathogenic flavivirus in China and Southeast Asia with features of rapid spread, an expanding host range, and cross-species transmission. The mechanisms of its infection and pathogenesis remain largely unclear. Here, we investigated the tropism of this arbovirus in peripheral blood mononuclear cells of specific-pathogen-free (SPF) ducks and SPF chickens and identified monocytes/macrophages as the key targets of TMUV infection. In vivo studies in SPF ducks and SPF chickens with monocyte/macrophage clearance demonstrated that the infection of monocytes/macrophages was crucial for viral replication, transmission, and pathogenesis. Further genome-wide transcriptome analyses of TMUV-infected chicken macrophages revealed that host antiviral innate immune barriers were the major targets of TMUV in macrophages. Despite the activation of major pattern recognition receptor signaling, the inductions of alpha interferon (IFN-γ) and IFN-δ were blocked by TMUV infection on transcription and translation levels, respectively. Meanwhile, TMUV inhibited host redox responses by repressing the transcription of genes encoding NADPH oxidase subunits and promoting Nrf2-mediated antioxidant responses. The recovery of either of the abovementioned innate immune barriers was sufficient to suppress TMUV infection. Collectively, we identify an essential step of TMUV infection and reveal extensive subversion of host antiviral innate immune responses. [ABSTRACT FROM AUTHOR]

Meretrix petechialis is an important commercial aquaculture species in China. During the clam culture period, mass mortality events often occurred due to the Vibrio infection. In this paper, M. petechialis were challenged with Vibrio parahaemolyticus immersion to simulate a natural infection, and the infection process were divided into four phases including latency, prodrome, onset and recovery phases based on the clam mortality data. Then, the dynamic response of clams to Vibrio infection at different infection phases were investigated by transcriptome analysis. A total of 38,067 differentially expressed genes (DEGs) were identified at different infection phases. DEG annotations showed that immune-related and metabolism-related signaling pathways were enriched, indicating that immune defense and metabolism process play key roles during bacterial infection. Three kinds of expression pattern were classified by cluster analysis, including U-shape, L-shape and inverted V-shape. Anabolism and cellular growth proliferation related signaling pathways were repressed (long-lasting or transient) during bacterial infection. However, the immune related signaling pathways with different immune functions showed induction expression or repression expression against bacterial infection, which indicated that immune system take different strategies against bacterial infection. Furthermore, some signaling pathways such as PI3K-Akt signaling pathway both involved in immune defense and cell metabolism. This study provides a sight that the dynamic immunity and metabolic responses may be integrated to improve the host survival and shift more energy for immune defense. • Four infection phases were divided based on clam mortality data after vibrio challenge. • Transcriptome analysis revealed the dynamic response of clam during infection. • The immune-related signaling pathways implement different strategies against vibrio infection. • An anabolism suppression was found response to bacterial infection. [ABSTRACT FROM AUTHOR]

Mud crabs, Scylla paramamosain , are one of the most economical and nutritious crab species in China and South Asia. Inconsistent with the high development of commercial mud crab aquaculture, effective immunological methods to prevent frequently-occurring diseases have not yet been developed. Thus, high mortalities often occur throughout the different developmental stages of this species resulting in large economic losses. In recent years, numerous attempts have been made to use various advanced biological technologies to understand the innate immunity of S. paramamosain as well as to characterize specific immune components. This review summarizes these research advances regarding cellular and humoral responses of the mud crab during pathogen infection, highlighting hemocytes and gills defense, pattern recognition, immune-related signaling pathways (Toll, IMD, JAK/STAT, and prophenoloxidase (proPO) cascades), immune effectors (antimicrobial peptides), production of reactive oxygen species and the antioxidant system. Diseases affecting the development of mud crab aquaculture and potential disease control strategies are discussed. Image 1 • Hemocytes and gills immune defenses are reviewed in the mud crab Scylla paramamosain. • Knowledge of pattern recognition and immune-related signaling pathways is updated. • Humoral responses, both immune effectors and antioxidant function, are described. • Strategies are proposed for disease mitigation and control in mud crab aquaculture. [ABSTRACT FROM AUTHOR]

Mandarin fish (Siniperca chuatsi) is a universally farmed fish species in China and has a large farming scale and economic value. With the high-density cultural mode in mandarin fish, viral diseases, such as infectious spleen and kidney necrosis virus (ISKNV) and Siniperca chuatsi rhabdovirus (SCRV), have increased loss, which has seriously restricted the development of aquaculture. Y-Box binding protein 1 (YB-1) is a member of cold shock protein family that regulates multiple cellular processes. The roles of mammalian YB-1 protein in environmental stress and innate immunity have been studied well, but its roles in teleost fishes remain unknown. In the present study, the characteristic of S. chuatsi YB-1 (sc YB-1) and its roles in cold stress and virus infection were investigated. The sc YB-1 obtained an 1541 bp cDNA that contains a 903 bp open reading frame encoding a protein of 300 amino acids. Tissue distribution results showed that the sc YB-1 is a ubiquitously expressed gene found among tissues from mandarin fish. Overexpression of sc YB-1 can increase the expression levels of cold shock-responsive genes, such as scHsc70a , scHsc70b , and scp53. Furthermore, the role of sc YB-1 in innate immunity was also investigated in mandarin fish fry (MFF-1) cells. The expression level of sc YB-1 was significant change in response to poly (I:C), poly (dG:dC), PMA, ISKNV, or SCRV stimulation. The overexpression of sc YB-1 can significantly increase the expression levels of NF-κB-responsive genes, including scIL-8, scTNF-α , and scIFN-h. The NF-κB-luciferase report assay results showed that the relative expression of luciferin was significantly increased in the cells overexpressed with sc YB-1 compared with those in cells overexpressed with control plasmid. These results indicate that sc YB-1 can induce the NF-κB signaling pathway in MFF-1 cells. Overexpressed sc YB-1 can downregulate the expression of ISKNV viral major capsid protein (mcp) gene but upregulates the expression of SCRV mcp gene. Moreover, knockdown of sc YB-1 using siRNA can upregulate the expression of ISKNV mcp gene but downregulates the expression of SCRV mcp gene. These results indicate that sc YB-1 suppresses ISKNV infection while enhancing SCRV infection. The above observations suggest that sc YB-1 is involved in cold stress and virus infection. Our study will provide an insight into the roles of teleost fish YB-1 protein in stress response and innate immunity. • S. chuatsi YB-1 (sc YB-1) is involved in the cold stress response in mandarin fish. • sc YB-1 can regulate the NF-κB signaling pathway in MFF-1 cells. • sc YB-1 suppresses ISKNV infection but enhances SCRV infection. [ABSTRACT FROM AUTHOR]

Tiger puffer (Takifugu rubripes) is one of the major aquaculture fish species in China due to its high economic value. In this study, the transcriptions of hepatic antioxidant enzyme, stress, apoptosis, and immune-related genes of sub-adult tiger puffers (Takifugu rubripes) were evaluated under two different rearing systems [offshore sea cage aquaculture system (OSCS) and recirculating aquaculture system (RAS)]. Results showed that the mRNA expression levels of the antioxidant enzyme (mn-sod , cu/zn-sod , gpx , and gr) and stress-related (hsp70 and hsp90) genes of male tiger puffers reared in the OSCS were significantly higher than female fish reared in the OSCS and fish reared in the RAS. The anti-apoptotic gene bcl2 exhibited the similar results. By contrast, the mRNAs of the pro-apoptotic genes (p53 , caspase8 , caspase9 , and caspase3) of male tiger puffers reared in the OSCS were significantly lower than female fish reared in the OSCS and fish reared in the RAS. Male tiger puffers reared in the OSCS displayed significantly higher complement components (c3) and inflammatory cytokine (il-6) mRNAs, whereas B-cell activating factor (baf) and tumor necrosis factor α (tnf-α) mRNAs remained unchanged. Meanwhile, the mRNA levels of pro-apoptotic (bax , caspase8) and immunity-related (c3, il-6 and il-7) genes of female tiger puffers reared in the OSCS were significantly lower and higher than female fish reared in the RAS, respectively. In conclusion, the hepatic antioxidant, anti-apoptosis, and innate immunity of tiger puffers reared in the OSCS were better than fish in the RAS, male tiger puffer obtained the best values. These results expand the knowledge on the combined RAS and OSCS alternative aquaculture model for tiger puffers and aid in their management in captive. • Comparison of hepatic oxidative stress, apoptosis and innate-immunity of sub-adult tiger puffer from two culture system. • Fish in the OSCS obtained the higher anti-apoptotic, anti-oxidative，immunity-related genes expression than in the RAS. • Male tiger puffer in the OSCS obtained the best values of aforementioned parameters. [ABSTRACT FROM AUTHOR]

Myeloid differentiation factor 88 (MyD88) links members of the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily to the downstream activation of NF-κB as a "bridge" molecular in response to exogenous pathogen, but the function in spotted knifejaw (Oplegnathus. punctatus), a commercial fish in China, is still unknown. We present a functional analysis of spotted knifejaw MyD88 (OppMyD88) with a typical death domain (DD) at the N-terminus and a conservative Toll/IL-1R (TIR) domain at the C-terminus and suggest that MyD88 is important for the activation of TLR-mediated NF-κB with the synergy between domains. Subcellular localization showed that OppMyD88 was distributed in the cytoplasm in a condensed form. Tissues expression profiling analysis showed that OppMyD88 ubiquitously expressed in all tested tissues with the highest expression in the liver, as determined by real-time PCR. The expression of OppMyD88 significantly upregulated in the liver, spleen, kidney and gills within 120 h post Vibrio anguillarum infection. Moreover, we further confirmed that over-expressed OppMyD88 could also induce apoptosis. These results indicate that OppMyD88 might possess important roles in defense against microbial infection and other biological processes in spotted knifejaw similar to those in mammals, which will deepen our understandings in innate immunity of spotted knifejaw. • A MyD88 homologue was isolated and characterized from O. punctatus (OppMyD88). • The gene structure and protein motifs of OppMyD88 were highly conserved among vertebrate. • OppMyD88 could be significantly induced in response to V. anguillarum infection. • OppMyD88 located in cytoplasm and can fully activate NF-κB under the joint action of structural domains. • OppMyD88 could induce apoptosis of HEK-293T cells relies on its death domain. [ABSTRACT FROM AUTHOR]

Abstract As an important economical shellfish in coastal area of China, abalone is susceptible to bacterial infection, especially Vibiro parahemolyticus (V. parahemolyticus). Matrix metalloproteinases (MMPs) have been extensively investigated in the immune response of mammals. However, little is known about the involvement of MMP in abalone innate immune system against pathogen infection. In this study, the role of MMP-1 in the immune response of Pacific abalone (Haliotis discus hannai) was explored. The results showed that V. parahemolyticus infection induced significantly elevated expression of MMP-1 as well as immune related genes including allograft inflammatory factor 1 (AIF-1), macrophage expressed gene 1 (MPEG-1) and TPA-inducible sequence 11 family protein (Tis11FP). Notably, silencing of MMP-1 reduced the expression of these genes, suggesting that MMP-1 was an upstream regulatory factor in V. parahemolyticus infection. Further analysis showed that MMP-1 was engaged in the regulation of cellular (phagocytosis, apoptosis) and humoral [superoxide dismutase (SOD), alkaline phosphatase (ALP), acid phosphatase (ACP)] immunity. Interestingly, the extracellularly distributed MMP-1 could be translocated to the nuclei of hemocytes, thereby functioning as a transcriptional regulator or by selectively activating or inactivating other components through proteolysis. Hence, our study established an important role of MMP-1 in abalone innate immunity against V. parahemolyticus infection and it represented the first report on the investigation of MMP in abalone. Highlights • Induced expression of MMP-1 was observed after Vibrio parahemolyticus infection in Pacific abalone (Haliotis discus hannai). • MMP-1 was involved in the regulation of phagocytosis and apoptosis activities in abalone. • SOD, ALP and ACP activities were regulated by MMP-1 in abalone. • MMP-1 altered the expression of AIF-1, MPEG-1 and Tis11FP genes. • MMP-1 could be translocated into the nuclei of abalone hemocytes post bacterial infection. [ABSTRACT FROM AUTHOR]

We have shown that human alveolar lining fluid (ALF) contains homeostatic hydrolases capable of altering the Mycobacterium tuberculosis cell wall and subsequently its interaction with human macrophages. Neutrophils are also an integral part of the host immune response to M. tuberculosis infection. Here we show that the human lung mucosa influences M. tuberculosis interaction with neutrophils, enhancing the intracellular killing of ALFexposed M. tuberculosis and up-regulating the expression of tumor necrosis factor and interleukin 8. In contrast, ALF-exposed M. tuberculosis does not induce neutrophil apoptosis or necrosis, degranulation, or release of extracellular traps, and it decreases the oxidative response. These results suggest an important role for the human alveolar mucosa: increasing the innate capacity of the neutrophil to recognize and kill M. tuberculosis by favoring the use of intracellular mechanisms, while at the same time limiting neutrophil extracellular inflammatory responses to minimize their associated tissue damage. [ABSTRACT FROM AUTHOR]

Infectious coryza (IC) is an acute infectious upper respiratory disease in chickens. Recently, the prevalence of IC has increased in China. In this study, to clarify the pathogenic mechanism and innate immune response of Avibacterium paragallinarum (A. paragallinarum), an infection experiment with A. paragallinarum was conducted. Our results showed that the whole course of IC was approximately 7 d. The clinical signs score was highest at 3 dpi and decreased from 5 dpi. A large amount of mucus and exudates was found in the infraorbital sinuses and nasal cavity. The A. paragallinarum contents in blood remained the highest, reaching 9.16 × 105 CFU/g at 5 dpi, which indicated that A. paragallinarum could rapidly invade the host, replicate in the blood and cause bacteremia. A. paragallinarum targets the upper respiratory tract. The infiltration of inflammatory cells, macrophages, and heterophilic granulocytes was only observed in the nasal cavity and infraorbital sinus. The Tlr4 and Nod1 pathways were activated and induced proinflammatory responses in chickens after infection with A. paragallinarum. The expression of Il1β and Il6 in the nasal cavity was significantly higher than that in the spleen, and it was consistent with the gross lesions and pathological changes. In particular, the expression of Il6 increased 229.07-fold at 1 dpi in the nasal cavity and increased 3.12-fold in the spleen. The high level of proinflammatory cytokines in the nasal cavity at an early stage of infection may be the main factor related to acute upper respiratory inflammation in chickens. These findings provide a reference for the occurrence and development of diseases mediated by A. paragallinarum. [ABSTRACT FROM AUTHOR]

Radix isatidis (R. isatidis) is a commonly used traditional Chinese herbal medicine, which has been used for thousands of years in China and is believed to have the pharmacological properties of heat-clearing and detoxification. Heat-clearing and detoxification are theories of traditional Chinese medicine meaning that R. isatidis could treat febrile disease by clearing heat and reducing swelling. Polysaccharides isolated from R. isatidis by water extraction and alcohol precipitation have exhibited numerous biological activities, including antiviral and immunomodulatory effects. The present study was performed to investigate the immunomodulatory effects of water-soluble R. isatidis polysaccharides (RIPs) on RAW264.7 macrophages and murine splenocytes, and attempt to preliminarily identify the mechanism of immunomodulation. In vitro, RIPs had a low cytotoxicity, as shown by CellTiter 96® AQueous One Solution Cell Proliferation Assay. RAW264.7 cells treated with different concentrations of RIP displayed different morphological changes, from a round shape and aggregation to polygonal shape and dispersion in a dose-dependent manner. In the 5 mg/ml RIP-treated group, the changes of morphology were as same as the lipopolysaccharide-treated group. RIP also significantly enhanced the release of nitric oxide as shown by Griess method, and the secretion of TNF-α and IL-6 in RAW264.7 cells was confirmed by ELISA assay. Western blotting revealed a significant increase of toll-like receptor-4 (TLR-4) in RIP-treated RAW264.7, suggesting that TLR-4 may be associated with the immunomodulatory mechanism of RIP. Animal experiments also demonstrated through ELISA assays a significant increase in IFN-γ and IL-10 levels after the splenocytes of RIP-immunized mice were stimulated by inactivated herpes simplex virus type 2. The immune function of RIP-immunized mice was improved. The present study suggested that RIP could be potentially used as a novel immunomodulator. [ABSTRACT FROM AUTHOR]

• ASFV genes show time-dependent expression patterns in infected PAMs. • ASFV potentially generates viral small RNAs. • ASFV infection strongly inhibits host immune response and triggers dysregulation of host chemokine axis and metabolic pathways. • ASFV infection leads to a unique transcriptome profile that differs from that for HP-PRRSV infection. African swine fever virus (ASFV), one of the most devastating emerging swine pathogens in China, causes nearly 100 % mortality in naive herds. Here, whole-transcriptome RNA-seq analysis was conducted in porcine alveolar macrophages (PAMs) infected with Pig/Heilongjiang/2018 (Pig/HLJ/18) ASFV at different time points. Our data suggested that ASFV genes expression demonstrated a time-depended pattern and ASFV early genes were involved in antagonizing host innate immunity. Moreover, viral small RNA (vsRNA) was generated as well. Meanwhile, transcriptome analysis of host genes suggested a strong inhibition host immunity-related genes by ASFV infection in PAMs, while enhanced chemokine-mediated signaling pathways and neutrophil chemotaxis were observed in ASFV infected PAMs. Furthermore, ASFV infection also down-regulated host microRNAs (miRNAs) that putatively targeted viral genes, while also triggering dysregulation of host metabolism that promoted virus replication at transcription level. Most importantly, infection of PAMs with ASFV induced a different transcriptome pattern from that of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV), which is known to trigger a host cytokine storm. In conclusion, our transcriptome data implied that ASFV infection in PAMs appeared to be associated with strong inhibition of host immune responses, dysregulation of host chemokine axis and metabolic pathways. [ABSTRACT FROM AUTHOR]

Abstract: China is the largest fishery producer worldwide in term of its aquaculture output, and plays leading and decisive roles in international aquaculture development. To improve aquaculture output further and promote aquaculture business development, infectious diseases and immunity of fishes and other aquaculture species must be studied. In this regard, aquaculture proteomics has been widely carried out in China to get a better understanding of aquaculture host immunity and microbial pathogenesis as well as host–pathogen interactions, and to identify novel disease targets and vaccine candidates for therapeutic interventions. These proteomics studies include development of novel methods, assays, and advanced concepts in order to characterize proteomics mechanisms of host innate immune defense and microbial pathogenesis. This review article summarizes some recently published technical approaches and their applications to aquaculture proteomics with an emphasis on the responses of aquaculture animals to bacteria, viruses, and other aqua-environmental stresses, and development of broadly cross-protective vaccine candidates. The reviewed articles are those that have been published in international peer reviewed journals. [Copyright &y& Elsevier]

Abstract: While conducting experiments to investigate antimicrobial peptides of amphibians living in the Yunnan-Sichuan region of southwest China, a new family of antimicrobial peptides was identified from skin secretions of the rufous-spotted torrent frog, Amolops loloensis. Members of the new peptide family named amolopins are composed of 18 amino acids with a unique sequence, for example, NILSSIVNGINRALSFFG. By BLAST search, amolopins did no show similarity to any known peptides. Among the tested microorganisms, native and synthetic peptides only showed antimicrobial activities against Staphylococcus aureus ATCC2592 and Bacillus pumilus, no effects on other microorganisms. The CD spectroscopy showed that it adopted a structure of random combined with β-sheet in water, Tris–HCl or Tris–HCl-SDS. Several cDNAs encoding amolopins were cloned from the skin cDNA library of A. loloensis. The precursors of amolopin are composed of 62 amino acid residues including predicted signal peptides, acidic propieces, and mature antimicrobial peptides. The preproregion of amolopin precursor comprises a hydrophobic signal peptide of 22 residues followed by an 18 residue acidic propiece which terminates by a typical prohormone processing signal Lys-Arg. The preproregions of precursors are very similar to other amphibian antimicrobial peptide precursors but the mature amolopins are different from other antimicrobial peptide families. The remarkable similarity of preproregions of precursors that give rise to very different antimicrobial peptides in distantly related frog species suggests that the corresponding genes form a multigene family originating from a common ancestor. [Copyright &y& Elsevier]

Human β-defensin (HBD)-1 is constitutively expressed in the airway, and hBD-1 plays crucial roles in innate immunity against respiratory pathogens. Asthma was associated with DEFB1 polymorphisms in Caucasians. This study investigates whether three single nucleotide polymorphisms (SNPs) in 5′-untranslated region of DEFB1 are associated with asthma phenotypes in Chinese children. Subjects aged 5–18 years were recruited from general pediatric clinics. Plasma IgE concentrations were measured by immunoassays. DEFB1 SNPs were characterized by restriction fragment length polymorphism. In all, 305 asthmatics and 156 controls were recruited. For asthma diagnosis, atopy and plasma total IgE, higher percentages of subjects with these outcomes had the minor alleles −20A and −52G (P=0.041–0.0002). For log-transformed total IgE, the covariate was positive and significant for G-20A under recessive model (P=0.001) and for G-52A under both recessive and codominant models (P=0.008 and 0.035). The recessive model covariate was also positive and significant (P=0.020) for C-44G on peripheral blood eosinophil count. The GCA haplotype of DEFB1 was significantly associated with asthma (odds ratio (95% confidence interval): 1.64 (1.05–2.57); P=0.029). These results suggest that DEFB1 is a candidate gene for asthma and atopy in children.Genes and Immunity (2006) 7, 59–64. doi:10.1038/sj.gene.6364279; published online 5 January 2006 [ABSTRACT FROM AUTHOR]

Simple Summary: As a medicinal insect, Coridius chinensis contains many active polypeptides. Extracts from C. chinensis are usually complex and it is not clear which polypeptides are effective medicinal ingredients. In addition, we also need to figure out the functions of various immune effectors in the innate immunity of C. chinensis. To explore the function of lysozyme in C. chinensis, a lysozyme gene CcLys2 was screened and identified from the transcriptome data of C. chinensis. The results showed that CcLys2 had a typical domain of the c-type lysozyme, belonging to the H-branch of the c-type lysozyme. The lysozyme Cclys2 is an effective immune effector in the immune response of C. chinensis and can be stimulated by bacterial infection. Like typical c-type lysozyme, Cclys2 has lytic activity against Gram-positive bacteria. The research holds promise for functional annotation of similar proteins from other dinidoridae insects and provides the theoretical feasibility for the development of medicinal components in C. chinensis. Our results also provide data for further investigating the origin and evolution of insect lysozymes. Coridius chinensis is a valuable medicinal insect resource in China. Previous studies have indicated that the antibacterial and anticancer effects of the C. chinensis extract mainly come from the active polypeptides. Lysozyme is an effective immune effector in insect innate immunity and usually has excellent bactericidal effects. There are two kinds of lysozymes in insects, c-type and i-type, which play an important role in innate immunity and intestinal digestion. Studying lysozyme in C. chinensis will be helpful to further explore the evolutionary relationship and functional differences among lysozymes of various species and to determine whether they have biological activity and medicinal value. In this study, a lysozyme CcLys2 was identified from C. chinensis. CcLys2 contains 223 amino acid residues, and possesses a typical domain of the c-type lysozyme and a putative catalytic site formed by two conserved residues Glu32 and Asp50. Phylogenetic analysis showed that CcLys2 belongs to the H-branch of the c-type lysozyme. The analysis of spatiotemporal expression patterns indicated that CcLys2 was mainly expressed in the fat body of C. chinensis adults and was highly expressed in the second- and fifth-instar nymphs. In addition, CcLys2 was significantly up-regulated after injecting and feeding bacteria. In the bacterial inhibition assay, it was found that CcLys2 had antibacterial activity against Gram-positive bacteria at a low pH. These results indicate that CcLys2 has muramidase activity, involves in the innate immunity of C. chinensis, and is also closely related to the bacterial immune defense or digestive function of the intestine. [ABSTRACT FROM AUTHOR]

The Novel Coronavirus Disease 2019 (COVID-19) has swept the world and caused a global pandemic. SARS-CoV-2 seems to have originated from bats as their reservoir hosts over time. Similar to SARS-CoV, this new virus also exerts its action on the human angiotensin-converting enzyme 2. This action causes infections in cells and establishes an infectious disease, COVID-19. Against this viral invasion, the human body starts to activate the innate immune system in producing and releasing proinflammatory cytokines such as IL-6, IL-1β, IL-8, TNF-α, and other chemokines, such as G-CSF, IP10 and MCPl, which all develop and increase the inflammatory response. In cases of COVID-19, excessive inflammatory responses occur, and exaggerated proinflammatory cytokines and chemokines are detected in the serum, resulting in cytokine release syndrome or cytokine storm. This causes coagulation abnormalities, excessive oxidation developments, mitochondrial permeability transition, vital organ damage, immune system failure and eventually progresses to disseminated intravascular coagulation and multiple organ failure. Additionally, the excessive inflammatory responses also cause mitochondrial dysfunction due to progressive and persistent stress. This damages cells and mitochondria, leaving products containing mitochondrial DNA and cell debris involved in the excessive chronic inflammation as damage-associated molecular patterns. Thus, the respiratory infection progressively leads to disseminated intravascular coagulation from acute respiratory distress syndrome, including vascular endothelial cell damage and coagulation-fibrinolysis system disorders. This condition causes central nervous system disorders, renal failure, liver failure and, finally, multiple organ failure. Regarding treatment for COVID-19, the following are progressive and multiple steps for mitigating the excessive inflammatory response and subsequent cytokine storm in patients. First, administering of favipiravir to suppress SARS-CoV-2 and nafamostat to inhibit ACE2 function should be considered. Second, anti-rheumatic drugs (monoclonal antibodies), which act on the leading cytokines (IL-1β, IL-6) and/or cytokine receptors such as tocilizumab, should be administered as well. Finally, melatonin may also have supportive effects for cytokine release syndrome, resulting in mitochondrial function improvement. This paper will further explore these subjects with reports mostly from China and Europe. [ABSTRACT FROM AUTHOR]

Macrobrachium rosenbergii , the giant freshwater prawn, is an important aquaculture species in China and other Southeast Asian countries. Here, we report the positive effect of dietary betaine supplementation on growth performance and the innate immune system in M. rosenbergii. Four diets were formulated containing graded levels of betaine, and a 10-week feeding trial was conducted. Prawns fed a diet containing 0.5% betaine (B 0.5) showed significantly higher growth performance, while feed efficiency was not significantly influenced compared with the control group. Moreover, the survival rate under bacterial challenge in the B 0.5 group was significantly higher than in the control group infected. Betaine supplementation also significantly reduced crude lipid content and significantly increased crude protein content in the B 0.5 and B 1 groups. Similarly, the contents of total (essential) amino acids and many flavorful amino acids such as Aspartic, Serine, Alanine and Glycine in the muscle were also significantly higher than in the control group. Most interestingly, the contents of n-3 PUFA and n-3 LC-PUFA in all betaine supplementation groups were significantly higher than in the control group. In addition, significantly higher activities were detected in the B 0.5 group than in the control group for hepatopancreas digestive enzymes Pepsin, Trypsin and Lipase, and serum enzymes including CAT, SOD, and TNF-α. We also checked the expression levels of five immune-related genes and found that Relish, TLR-1, and TLR-2 were all significantly down regulated in all supplementation groups, while HSP70 was significantly upregulated only in the B 0.5 group. Taken together, our results demonstrated that a moderate amount of dietary betaine supplementation not only promotes growth but also benefits the innate immune system of M. rosenbergii. • Betaine supplementation significantly improved crude protein content and flavor amino acid content in the B 0.5 group. • Dietary betaine significantly reduced crude lipid content but significantly increased n-3 PUFA content in the muscle. • Both innate immunity and survival rate under bacterial challenge were enhanced by betaine supplementation at 0.5% level. • Dietary betaine significantly improved the activity of most hepatopancreas digestive enzymes in the B 0.5 group. [ABSTRACT FROM AUTHOR]

The innate immune system is the first line of defense protecting the hosts against invading pathogens. Mud crab (Scylla paramamosain) is widely distributed in China and Indo-west Pacific countries, which develops a very complicated innate immune system against pathogen invasions. Innate immunity involves the humoral and cellular responses that are linked to the pattern recognition receptors (PRRs). PRRs initially recognize the infection and trigger the activation of signaling cascades, leading to transcriptional regulation of inflammatory mediators that function in pathogenic control and clearance. In mud crab S. paramamosain , the Toll/Toll-like receptors, lipopolysaccharide and β-1,3-glucan binding proteins, C-type lectins, scavenger receptors, and down syndrome cell adhesion molecules have been identified as receptor families responsible for the recognition of bacteria, fungi, and viruses, and are important components in the innate immune system. In this review, we summarize the literature on the current knowledge and the roles of PRRs in the immune defenses of mud crab, which in an effort to provide much information for further researches. • Five pattern recognition receptors (PRRs) have been reported in mud crab. • Different PRRs target to different ligands in the innate immunity. • PRRs activate the intracellular signaling cascades and subsequently respond to the infections. [ABSTRACT FROM AUTHOR]

Duck tembusu virus (DTMUV) is a single-stranded, positive-polarity RNA flavivirus that has caused considerable economic losses in China in recent years. Innate immunity represents the first line of defense against invading pathogens and serves as an important role in resisting viral infections. In this study, we found that the infection of ducks by DTMUV triggers Toll-like receptors (TLRs) and (RIG-I)-like receptors (RLRs) signaling pathways and inducing abundant of pro-inflammatory factors and type I interferons (IFNs), in which melanoma differentiation-associated gene 5 (MDA5) and Toll-like receptor 3 (TLR3) play important immunity roles, they can inhibit the replication process of DTMUV via inducing type I IFNs. Moreover, we demonstrated that type I IFNs can inhibit the DTMUV replication process in a time- and dose-dependent manner. Exosomes are small membrane vesicles that have important roles in intercellular communication. MicroRNAs (miRNAs) are small non-coding RNAs that can modulate gene expression and are common substances in exosomes. In our experiment, we successfully isolated DEF cells derived exosome for the first time and explored its function. Firstly, we found the expression of miR-148a-5p is significantly decreased following DTMUV infect. Then we found miR-148a-5p can target TLR3 and down-regulate the expression of TLR3, serving as a negative factor in innate immunity. Unfortunately, we cannot find miRNAs with different expression changes that can target MDA5. Lastly, our experimental results showed that TLR3 was one of the causes of miR-148a-5p reduction, suggesting that the high level of TLR3 after DTMUV infect can both trigger innate immunity and suppress miR-148a-5p to resist DTMUV. [ABSTRACT FROM AUTHOR]

Astroviral infection is considered to be one of the causes of mammalian diarrheal diseases. It has been shown that astrovirus infections cause varying degrees of diarrhea in turkeys and mice. However, the pathogenesis of porcine astrovirus is unknown. In this study, the virulence of a cytopathic porcine astrovirus (PAstV) strain (PAstV1-GX1) isolated from the PK-15 cell line was tested using seven-day-old nursing piglets. The results showed that PAstV1-GX1 infection could cause mild diarrhea, growth retardation, and damage of the villi of the small intestinal mucosa. However, all the above symptoms could be restored within 7 to 10days post inoculation (dpi). To evaluate the innate immunity response of PAstV in vivo, the alteration of inflammatory cytokine expression in piglets infected with PAstV1-GX1 was determined using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The mRNA expression levels of the IFNβ and ISG54 were found to be significantly elevated in virus-infected piglets. In contrast, expression of IFNλ was downregulated in piglets infected with PAstV1-GX1. In addition, the mRNA expression of the tight junction protein 1 and 2 and zonula occludin 1, which are associated with the intestinal barrier permeability, were affected after PAstV1 infection. The present study adds to our understanding of the pathogenic mechanism of PAstV and has established an animal model for further study of pig astrovirus infection. [ABSTRACT FROM AUTHOR]