In the current study,tea saponin,identified as the primary bioactive constituent in seed pomace of Camellia oleifera Abel.,was meticulously extracted and hydrolyzed to yield five known sapogenins:16-O-tiglogycamelliag...In the current study,tea saponin,identified as the primary bioactive constituent in seed pomace of Camellia oleifera Abel.,was meticulously extracted and hydrolyzed to yield five known sapogenins:16-O-tiglogycamelliagnin B(a),camelliagnin A(b),16-O-angeloybarringtogenol C(c),theasapogenol E(d),theasapogenol F(e).Subsequent biotransformation of compound a facilitated the isolation of six novel metabolites(a1−a6).The anti-inflammatory potential of these compounds was assessed using pathogenassociated molecular patterns(PAMPs)and damage-associated molecular patterns molecules(DAMPs)-mediated cellular inflammation models.Notably,compounds b and a2 demonstrated significant inhibitory effects on both lipopolysaccharide(LPS)and high-mobility group box 1(HMGB1)-induced inflammation,surpassing the efficacy of the standard anti-inflammatory agent,carbenoxolone.Conversely,compounds d,a3,and a6 selectivity targeted endogenous HMGB1-induced inflammation,showcasing a pronounced specificity.These results underscore the therapeutic promise of C.oleifera seed pomace-derived compounds as potent agents for the management of inflammatory diseases triggered by infections and tissue damage.展开更多
Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive imm...Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.展开更多
A turbot(Scophthalmus maximus)cell line named SMSP was obtained from the spleen.The origin of the cells was identified by morphology,chromosome number and COI gene.The optimal basic medium,serum concentration and grow...A turbot(Scophthalmus maximus)cell line named SMSP was obtained from the spleen.The origin of the cells was identified by morphology,chromosome number and COI gene.The optimal basic medium,serum concentration and growth temperature of the cells were detected.SMSP cell line is mainly composed of fibroblast-like cells.Most of the SMSP cells contained 44 chromosomes,and the sequence of COI gene confirmed that the cells were originated from turbot.The optimal culture conditions were 24℃,DMEM+10%FBS.The cell line had high transfection efficiency for siRNA and plasmid.After stimulation with lipopolysaccharide(LPS)or poly(I:C),the expressions of immune-related genes such as TNF-β,IL-12s,IL-10 and IL-1βwere up-regulated significantly in the early stage(P<0.05).This study will provide a model for exploring immune mechanism of turbot against pathogen in vitro.展开更多
Receptor-like kinases(RLKs)and receptor-like cytoplasmic kinases(RLCKs)play an indispensable role in the perception and transmission of extracellular signals in plants.In rice,these kinases actively participate in imm...Receptor-like kinases(RLKs)and receptor-like cytoplasmic kinases(RLCKs)play an indispensable role in the perception and transmission of extracellular signals in plants.In rice,these kinases actively participate in immune responses against a variety of pathogens,including fungi,bacteria,and viruses.However,research on the specific response mechanisms and the spectrum of different kinase activities against various pathogens remains insufficient.This review provides an in-depth and comprehensive overview of the types and functions of RLKs and RLCKs involved in disease resistance,emphasizing the central role of certain RLKs and RLCKs in the plant immune system.These kinases can recognize specific molecular patterns of pathogens and rapidly initiate an immune response in rice.Furthermore,the activity and functional regulation of these key kinases are tightly controlled by various post-translational modifications,such as phosphorylation and ubiquitination.This meticulous regulation ensures that the rice immune system's response is both precise and timely,effectively balancing the intensity of the immune response and preventing potential issues caused by either hyperactivity or insufficiency.By synthesizing current research findings,this review not only broadens our understanding of the role of RLKs and RLCKs in plant immunity but also provides new perspectives and strategies for future research on disease resistance breeding in rice.Future studies are expected to delve deeper into the signaling networks and regulatory mechanisms of these kinases,exploring their potential in agricultural production to develop rice varieties with enhanced disease resistance.展开更多
Helicobacter pylori(H.pylori)infects the human stomach during infancy and develops into chronic activeinflammation.The majority of H.pylori tend to colonize within the mucous gel layer of the stomach.Thestomach lacks ...Helicobacter pylori(H.pylori)infects the human stomach during infancy and develops into chronic activeinflammation.The majority of H.pylori tend to colonize within the mucous gel layer of the stomach.Thestomach lacks its own immune function,thus innateimmunity as the first line of defense is vital for specificimmunity against H.pylori.We review recent discoveries in the pathophysiologic roles of toll-like receptors(TLRs),mainly TLR2 and TLR4,in H.pylori-induced inflammation.In addition,the TLR pathways activated byH.pylori-induced inflammation have been shown to beclosely associated not only with gastric carcinogenesis,but also with formation of the tumor microenvironmentthrough the production of pro-inflammatory cytokines,chemokines,and reactive oxygen species.Althoughthe correlation between single nucleotide polymorphisms of TLRs and gastric cancer risk remains unclear,a recent study demonstrated that STAT3-driven upregulation of TLR2 might promote gastric tumorigenesis independent of inflammation.Further research onthe regulation of TLRs in H.pylori-associated gastriccarcinogenesis will uncover diagnostic/predictive biomarkers and therapeutic targets for gastric cancer.展开更多
Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understo...Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that sequentially release early(e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-γ(IFN-γ) and late(e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late mediator of inflammatory diseases and discuss the potential of several Chinese herbal components as HMGB1-targeting therapies. We propose that it is important to develop strategies for specifically attenuating injury-elicited inflammatory responses without compromising the infection-mediated innate immunity for the clinical management of sepsis and other inflammatory diseases.展开更多
Hepatitis D virus(HDV)is a global health threat with more than 15 million humans affected.Current treatment options are largely unsatisfactory leaving chronically infected humans at high risk to develop liver cirrhosi...Hepatitis D virus(HDV)is a global health threat with more than 15 million humans affected.Current treatment options are largely unsatisfactory leaving chronically infected humans at high risk to develop liver cirrhosis and hepatocellular carcinoma.HDV is the only human satellite virus known.It encodes only two proteins,and requires Hepatitis B virus(HBV)envelope protein expression for productive virion release and spread of the infection.How HDV could evolve and why HBV was selected as a helper virus remains unknown.Since the discovery of Na+-taurocholate co-transporting polypeptide as the essential uptake receptor for HBV and HDV,we are beginning to understand the interactions of HDV and the immune system.While HBV is mostly regarded a stealth virus,that escapes innate immune recognition,HBV-HDV coinfection is characterized by a strong innate immune response.Cytoplasmic RNA sensor melanoma differentiation antigen 5 has been reported to recognize HDV RNA replication and activate innate immunity.Innate immunity,however,seems not to impair HDV replication while it inhibits HBV.In this review,we describe what is known up-to-date about the interplay between HBV as a helper and HDV’s immune evasion strategy and identify where additional research is required.展开更多
As an aquatic fish,the spotted halibut Verasper variegatus is highly susceptible to bacterial and virus infections.Tumor necrosis factor-alpha(TNF-α)as a cytokine could control the inflammatory responses.The function...As an aquatic fish,the spotted halibut Verasper variegatus is highly susceptible to bacterial and virus infections.Tumor necrosis factor-alpha(TNF-α)as a cytokine could control the inflammatory responses.The functions of TNF-αin many species have been widely studied,particularly in mammals.However,little is known about the TNF-αfunctions in V.variegatus.We first cloned and sequenced the TNF-αgene in V.variegatus(VvTNF-α).The two conserved cysteine residues,transmembrane sequence,Thr-Leu motif,and TNF family signature,as well as the TA-rich motifs of its proteins related to inflammatory responses had high similarity to those of the other teleost and mammalian TNF-α.The phylogenetic analysis showed that VvTNF-αwas consistent with TNF-αgenes of other vertebrates.The VvTNF-αtranscripts were extensively distributed in the peripheral blood leukocytes(PBLs),spleen,and gill,indicating that the VvTNF-αhad a role in immune function.Furthermore,treatment with pathogen-associated molecular patterns(PAMPs)could induce a rapid and significant increase of VvTNF-αin the PBLs,which reveals that VvTNF-αdoes participate in the host immune responses against bacterial and viral pathogens.We found that VvTNF-αhad an interesting expression pattern during metamorphosis,showing that the flatfish TNF-αmay have some novel functions during specific developmental stages.In addition,the 3 D structure prediction of VvTNF-αprovided an indication of how it is likely to interact with other proteins.Therefore,VvTNF-αhas multiple functions,and provides valuable information to explore novel functions of TNF-α.展开更多
Production of reactive oxygen species(ROS)is a conserved immune response primarily mediated by NADPH oxidases(NOXs),also known in plants as respiratory burst oxidase homologs(RBOHs).Most microbe-associated molecular p...Production of reactive oxygen species(ROS)is a conserved immune response primarily mediated by NADPH oxidases(NOXs),also known in plants as respiratory burst oxidase homologs(RBOHs).Most microbe-associated molecular patterns(MAMPs)trigger a very fast and transient ROS burst in plants.However,recently,we found that lipopolysaccharides(LPS),a typical bacterial MAMP,triggered a biphasic ROS burst.In this study,we isolated mutants defective in LPS-triggered biphasic ROS burst(delt)in Arabidopsis,and cloned the DELT1 gene that was shown to encode RBOHD.In the delt1-2 allele,the antepenultimate residue,glutamic acid(E919),at the C-terminus of RBOHD was mutated to lysine(K).E919 is a highly conserved residue in NADPH oxidases,and a mutation of the corresponding residue E568 in human NOX2 has been reported to be one of the causes of chronic granulomatous disease.Consistently,we found that residue E919 was indispensable for RBOHD function in the MAMP-induced ROS burst and stomatal closure.It has been suggested that the mutation of this residue in other NADPH oxidases impairs the protein’s stability and complex assembly.However,we found that the E919K mutation did not affect RBOHD protein abundance or the ability of protein association,suggesting that the residue E919 in RBOHD might have a regulatory mechanism different from that of other NOXs.Taken together,our results confirm that the antepenultimate residue E is critical for NADPH oxidases and provide a new insight into the regulatory mechanisms of RBOHD.展开更多
Pathogen-associated molecular pattern(PAMP)-triggered immunity(PTI)is an essential layer of plant disease resistance.Robust bioassays for PTI are pre-required to dissect its molecular mechanism.In this study,we establ...Pathogen-associated molecular pattern(PAMP)-triggered immunity(PTI)is an essential layer of plant disease resistance.Robust bioassays for PTI are pre-required to dissect its molecular mechanism.In this study,we established that lateral root growth inhibition as a simple and robust measurement of PTI in rice seedlings.Specifically,flg22,a well-characterized PAMP from bacterial flagellin,was used to induce PTI in rice seedlings.While flg22 treatment induced PR gene expression and mitogen-activated protein kinase activation in the roots of rice seedlings to support the PTI triggered,this treatment substantially repressed lateral root growth,but it did not alter primary root growth.Moreover,treatments with chitin(i.e.,a fungal PAMP)and oligogalacturonides(i.e.,classical damage-associated molecular pattern)clearly inhibited the lateral root growth,although a priming step involving ulvan was required for the chitin treatment.The bioassay developed was applicable to various rice cultivars and wild species.Thus,lateral root growth inhibition represents a simple and reliable assay for studying PTI in rice plants.展开更多
Pyroptosis is the process of inflammatory cell death.The primary function of pyroptosis is to induce strong inflammatory responses that defend the host against microbe infection.Excessive pyroptosis,however,leads to s...Pyroptosis is the process of inflammatory cell death.The primary function of pyroptosis is to induce strong inflammatory responses that defend the host against microbe infection.Excessive pyroptosis,however,leads to several inflammatory diseases,including sepsis and autoimmune disorders.Pyroptosis can be canonical or noncanonical.Upon microbe infection,the canonical pathway responds to pathogen-associated molecular patterns(PAMPs) and damage-associated molecular patterns(DAMPs),while the noncanonical pathway responds to intracellular lipopolysaccharides(LPS) of Gram-negative bacteria.The last step of pyroptosis requires the cleavage of gasdermin D(GsdmD) at D275(numbering after human GSDMD) into N-and C-termini by caspase 1 in the canonical pathway and caspase 4/5/11(caspase 4/5 in humans,caspase 11 in mice) in the noncanonical pathway.Upon cleavage,the N-terminus of GsdmD(GsdmD-N) forms a transmembrane pore that releases cytokines such as IL-1β and IL-18 and disturbs the regulation of ions and water,eventually resulting in strong inflammation and cell death.Since GsdmD is the effector of pyroptosis,promising inhibitors of GsdmD have been developed for inflammatory diseases.This review will focus on the roles of GsdmD during pyroptosis and in diseases.展开更多
Plants employ a highly effective surveillance system to detect potential pathogens, which is critical for the success of land plants in an environment surrounded by numerous microbes. Recent efforts have led to the id...Plants employ a highly effective surveillance system to detect potential pathogens, which is critical for the success of land plants in an environment surrounded by numerous microbes. Recent efforts have led to the identification of a number of immune receptors and components of immune receptor complexes. It is now clear that receptor-like kinases （RLKs） and receptor-like proteins （RLPs） are key pattern-recognition receptors （PRRs） for microbe- and plant-derived molecular patterns that are associated with pathogen invasion. RLKs and RLPs involved in immune signaling belong to large gene families in plants and have undergone lineage specific expansion. Molecular evolution and population studies on phytopathogenic molecular signatures and their receptors have provided crucial insight into the co-evolution between plants and pathogens.展开更多
Interactions between plants and microbes result in plant disease and symbiosis. The former causes considerable economic damage in modern agriculture, while the latter has produced great beneficial effects to our agric...Interactions between plants and microbes result in plant disease and symbiosis. The former causes considerable economic damage in modern agriculture, while the latter has produced great beneficial effects to our agriculture system. Comparison of the two interactions has revealed that a common panel of signaling pathways might participate in the establishment of the equilibrium between plant and microbes or its break-up. Plants appear to detect both pathogenic and symbiotic microbes by a similar set of genes. All symbiotic microbes seem to produce effectors to overcome plant basal defenses and it is speculated that symbiotic effectors have functions similar to pathogenic ones. Signaling molecules, salicylic acid （SA）, jasmonic acid （JA） and ethylene （ET）, are involved in both plant defense and symbiosis. Switching off signals contributing to deterioration of disease symptom would establish a new equilibrium between plant and pathogenic microbes. This would facilitate the development of strategies for durable disease resistance.展开更多
Plants exploit several types of cell surface receptors for perception of extracellular signals, of which the extracellular leucine-rich repeat （eLRR）-containing receptors form the major class. Although the function ...Plants exploit several types of cell surface receptors for perception of extracellular signals, of which the extracellular leucine-rich repeat （eLRR）-containing receptors form the major class. Although the function of most plant eLRR receptors remains unclear, an increasing number of these receptors are shown to play roles in innate immunity and a wide variety of developmental processes. Recent efforts using domain swaps, gene shuffling analyses, site-directed mutagenesis, interaction studies, and crystallographic analyses resulted in the current knowledge on ligand binding and the mechanism of activation of plant eLRR receptors. This review provides an overview of eLRR receptor research, specificallysummarizing the recent understanding of interactions among plant eLRR receptors, their co-receptors and corresponding ligands. The functions of distinct eLRR receptor domains, and their role in structure, ligand perception and multimeric complex formation are discussed.展开更多
基金supported by the National Nature Science Foundation of China(No.21302052)the“Program for New Century Excellent Talents in University”awarded to ZHANG Jian(No.NECT-11-0739)+1 种基金the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.SJKY19_0658)Jiangsu Funding Program for Excellent Postdoctoral Talent,and“Jiangsu Funding Program for Excellent Postdoctoral Talent”awarded to SHEN Pingping.
文摘In the current study,tea saponin,identified as the primary bioactive constituent in seed pomace of Camellia oleifera Abel.,was meticulously extracted and hydrolyzed to yield five known sapogenins:16-O-tiglogycamelliagnin B(a),camelliagnin A(b),16-O-angeloybarringtogenol C(c),theasapogenol E(d),theasapogenol F(e).Subsequent biotransformation of compound a facilitated the isolation of six novel metabolites(a1−a6).The anti-inflammatory potential of these compounds was assessed using pathogenassociated molecular patterns(PAMPs)and damage-associated molecular patterns molecules(DAMPs)-mediated cellular inflammation models.Notably,compounds b and a2 demonstrated significant inhibitory effects on both lipopolysaccharide(LPS)and high-mobility group box 1(HMGB1)-induced inflammation,surpassing the efficacy of the standard anti-inflammatory agent,carbenoxolone.Conversely,compounds d,a3,and a6 selectivity targeted endogenous HMGB1-induced inflammation,showcasing a pronounced specificity.These results underscore the therapeutic promise of C.oleifera seed pomace-derived compounds as potent agents for the management of inflammatory diseases triggered by infections and tissue damage.
基金Supported by Shenzhen Medical Research Fund,No.D2301010Shenzhen Science and Technology Program,No.RCYX20231211090346060。
文摘Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.
基金the National Natural Science Foundation of China(No.31902403)the Young Experts of Taishan Scholars(No.tsqn201909130)+2 种基金the advanced Talents Foundation of QAU grant(No.663-1120029)the Shandong Technical System of Fish Industry(No.SDAIT-12-03)the Breeding Plan of Shandong Provincial Qingchuang Research Team(2019),China。
文摘A turbot(Scophthalmus maximus)cell line named SMSP was obtained from the spleen.The origin of the cells was identified by morphology,chromosome number and COI gene.The optimal basic medium,serum concentration and growth temperature of the cells were detected.SMSP cell line is mainly composed of fibroblast-like cells.Most of the SMSP cells contained 44 chromosomes,and the sequence of COI gene confirmed that the cells were originated from turbot.The optimal culture conditions were 24℃,DMEM+10%FBS.The cell line had high transfection efficiency for siRNA and plasmid.After stimulation with lipopolysaccharide(LPS)or poly(I:C),the expressions of immune-related genes such as TNF-β,IL-12s,IL-10 and IL-1βwere up-regulated significantly in the early stage(P<0.05).This study will provide a model for exploring immune mechanism of turbot against pathogen in vitro.
基金supported by the National Natural Science Foundation of China (Grant No.U2005211)the Fuzhou General Teaching Hospital (the 900th Hospital)Key Project,China (Grant No.2022ZD01)the Fujian Clinical Research Center for Aptamer-based Precision Testing,China (Grant No.2021Y2017)。
文摘Receptor-like kinases(RLKs)and receptor-like cytoplasmic kinases(RLCKs)play an indispensable role in the perception and transmission of extracellular signals in plants.In rice,these kinases actively participate in immune responses against a variety of pathogens,including fungi,bacteria,and viruses.However,research on the specific response mechanisms and the spectrum of different kinase activities against various pathogens remains insufficient.This review provides an in-depth and comprehensive overview of the types and functions of RLKs and RLCKs involved in disease resistance,emphasizing the central role of certain RLKs and RLCKs in the plant immune system.These kinases can recognize specific molecular patterns of pathogens and rapidly initiate an immune response in rice.Furthermore,the activity and functional regulation of these key kinases are tightly controlled by various post-translational modifications,such as phosphorylation and ubiquitination.This meticulous regulation ensures that the rice immune system's response is both precise and timely,effectively balancing the intensity of the immune response and preventing potential issues caused by either hyperactivity or insufficiency.By synthesizing current research findings,this review not only broadens our understanding of the role of RLKs and RLCKs in plant immunity but also provides new perspectives and strategies for future research on disease resistance breeding in rice.Future studies are expected to delve deeper into the signaling networks and regulatory mechanisms of these kinases,exploring their potential in agricultural production to develop rice varieties with enhanced disease resistance.
文摘Helicobacter pylori(H.pylori)infects the human stomach during infancy and develops into chronic activeinflammation.The majority of H.pylori tend to colonize within the mucous gel layer of the stomach.Thestomach lacks its own immune function,thus innateimmunity as the first line of defense is vital for specificimmunity against H.pylori.We review recent discoveries in the pathophysiologic roles of toll-like receptors(TLRs),mainly TLR2 and TLR4,in H.pylori-induced inflammation.In addition,the TLR pathways activated byH.pylori-induced inflammation have been shown to beclosely associated not only with gastric carcinogenesis,but also with formation of the tumor microenvironmentthrough the production of pro-inflammatory cytokines,chemokines,and reactive oxygen species.Althoughthe correlation between single nucleotide polymorphisms of TLRs and gastric cancer risk remains unclear,a recent study demonstrated that STAT3-driven upregulation of TLR2 might promote gastric tumorigenesis independent of inflammation.Further research onthe regulation of TLRs in H.pylori-associated gastriccarcinogenesis will uncover diagnostic/predictive biomarkers and therapeutic targets for gastric cancer.
基金supported by grants from the National Center of Complementary and Alternative Medicine (NCCAM, R01AT005076)the National Institute of General Medical Sciences (NIGMS, R01GM063075)
文摘Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that sequentially release early(e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-γ(IFN-γ) and late(e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late mediator of inflammatory diseases and discuss the potential of several Chinese herbal components as HMGB1-targeting therapies. We propose that it is important to develop strategies for specifically attenuating injury-elicited inflammatory responses without compromising the infection-mediated innate immunity for the clinical management of sepsis and other inflammatory diseases.
基金Supported by German Research Foundation,No. TRR 179
文摘Hepatitis D virus(HDV)is a global health threat with more than 15 million humans affected.Current treatment options are largely unsatisfactory leaving chronically infected humans at high risk to develop liver cirrhosis and hepatocellular carcinoma.HDV is the only human satellite virus known.It encodes only two proteins,and requires Hepatitis B virus(HBV)envelope protein expression for productive virion release and spread of the infection.How HDV could evolve and why HBV was selected as a helper virus remains unknown.Since the discovery of Na+-taurocholate co-transporting polypeptide as the essential uptake receptor for HBV and HDV,we are beginning to understand the interactions of HDV and the immune system.While HBV is mostly regarded a stealth virus,that escapes innate immune recognition,HBV-HDV coinfection is characterized by a strong innate immune response.Cytoplasmic RNA sensor melanoma differentiation antigen 5 has been reported to recognize HDV RNA replication and activate innate immunity.Innate immunity,however,seems not to impair HDV replication while it inhibits HBV.In this review,we describe what is known up-to-date about the interplay between HBV as a helper and HDV’s immune evasion strategy and identify where additional research is required.
基金Supported by the National High Technology Research and Development Program of China(863 Program)(No.31101891)the Hitech Research and Development Program of China(No.2012AA10A408)
文摘As an aquatic fish,the spotted halibut Verasper variegatus is highly susceptible to bacterial and virus infections.Tumor necrosis factor-alpha(TNF-α)as a cytokine could control the inflammatory responses.The functions of TNF-αin many species have been widely studied,particularly in mammals.However,little is known about the TNF-αfunctions in V.variegatus.We first cloned and sequenced the TNF-αgene in V.variegatus(VvTNF-α).The two conserved cysteine residues,transmembrane sequence,Thr-Leu motif,and TNF family signature,as well as the TA-rich motifs of its proteins related to inflammatory responses had high similarity to those of the other teleost and mammalian TNF-α.The phylogenetic analysis showed that VvTNF-αwas consistent with TNF-αgenes of other vertebrates.The VvTNF-αtranscripts were extensively distributed in the peripheral blood leukocytes(PBLs),spleen,and gill,indicating that the VvTNF-αhad a role in immune function.Furthermore,treatment with pathogen-associated molecular patterns(PAMPs)could induce a rapid and significant increase of VvTNF-αin the PBLs,which reveals that VvTNF-αdoes participate in the host immune responses against bacterial and viral pathogens.We found that VvTNF-αhad an interesting expression pattern during metamorphosis,showing that the flatfish TNF-αmay have some novel functions during specific developmental stages.In addition,the 3 D structure prediction of VvTNF-αprovided an indication of how it is likely to interact with other proteins.Therefore,VvTNF-αhas multiple functions,and provides valuable information to explore novel functions of TNF-α.
基金the National Natural Science Foundation of China(No.31622006)the Postdoctoral Science Foundation of China(Nos.2018M630683 and 2018T110601)
文摘Production of reactive oxygen species(ROS)is a conserved immune response primarily mediated by NADPH oxidases(NOXs),also known in plants as respiratory burst oxidase homologs(RBOHs).Most microbe-associated molecular patterns(MAMPs)trigger a very fast and transient ROS burst in plants.However,recently,we found that lipopolysaccharides(LPS),a typical bacterial MAMP,triggered a biphasic ROS burst.In this study,we isolated mutants defective in LPS-triggered biphasic ROS burst(delt)in Arabidopsis,and cloned the DELT1 gene that was shown to encode RBOHD.In the delt1-2 allele,the antepenultimate residue,glutamic acid(E919),at the C-terminus of RBOHD was mutated to lysine(K).E919 is a highly conserved residue in NADPH oxidases,and a mutation of the corresponding residue E568 in human NOX2 has been reported to be one of the causes of chronic granulomatous disease.Consistently,we found that residue E919 was indispensable for RBOHD function in the MAMP-induced ROS burst and stomatal closure.It has been suggested that the mutation of this residue in other NADPH oxidases impairs the protein’s stability and complex assembly.However,we found that the E919K mutation did not affect RBOHD protein abundance or the ability of protein association,suggesting that the residue E919 in RBOHD might have a regulatory mechanism different from that of other NOXs.Taken together,our results confirm that the antepenultimate residue E is critical for NADPH oxidases and provide a new insight into the regulatory mechanisms of RBOHD.
基金supported by the National Key Research and Development Program of China(Grant No.2016YFD0100602)the National Natural Science Foundation of China(Grant No.31901868)。
文摘Pathogen-associated molecular pattern(PAMP)-triggered immunity(PTI)is an essential layer of plant disease resistance.Robust bioassays for PTI are pre-required to dissect its molecular mechanism.In this study,we established that lateral root growth inhibition as a simple and robust measurement of PTI in rice seedlings.Specifically,flg22,a well-characterized PAMP from bacterial flagellin,was used to induce PTI in rice seedlings.While flg22 treatment induced PR gene expression and mitogen-activated protein kinase activation in the roots of rice seedlings to support the PTI triggered,this treatment substantially repressed lateral root growth,but it did not alter primary root growth.Moreover,treatments with chitin(i.e.,a fungal PAMP)and oligogalacturonides(i.e.,classical damage-associated molecular pattern)clearly inhibited the lateral root growth,although a priming step involving ulvan was required for the chitin treatment.The bioassay developed was applicable to various rice cultivars and wild species.Thus,lateral root growth inhibition represents a simple and reliable assay for studying PTI in rice plants.
基金supported by a grant from the National Institute of General Medical Sciences(P20 GM103429,USA)grants from National Heart,Lung and Blood Institute(HL153876,USA)National Eye Institute(EY030621,USA)
文摘Pyroptosis is the process of inflammatory cell death.The primary function of pyroptosis is to induce strong inflammatory responses that defend the host against microbe infection.Excessive pyroptosis,however,leads to several inflammatory diseases,including sepsis and autoimmune disorders.Pyroptosis can be canonical or noncanonical.Upon microbe infection,the canonical pathway responds to pathogen-associated molecular patterns(PAMPs) and damage-associated molecular patterns(DAMPs),while the noncanonical pathway responds to intracellular lipopolysaccharides(LPS) of Gram-negative bacteria.The last step of pyroptosis requires the cleavage of gasdermin D(GsdmD) at D275(numbering after human GSDMD) into N-and C-termini by caspase 1 in the canonical pathway and caspase 4/5/11(caspase 4/5 in humans,caspase 11 in mice) in the noncanonical pathway.Upon cleavage,the N-terminus of GsdmD(GsdmD-N) forms a transmembrane pore that releases cytokines such as IL-1β and IL-18 and disturbs the regulation of ions and water,eventually resulting in strong inflammation and cell death.Since GsdmD is the effector of pyroptosis,promising inhibitors of GsdmD have been developed for inflammatory diseases.This review will focus on the roles of GsdmD during pyroptosis and in diseases.
基金supported by grants from Chinese Natural Science Foundation (31230007)Chinese Ministry of Science and Technology (2011CB1007002011CB100702) to J.M.Z
文摘Plants employ a highly effective surveillance system to detect potential pathogens, which is critical for the success of land plants in an environment surrounded by numerous microbes. Recent efforts have led to the identification of a number of immune receptors and components of immune receptor complexes. It is now clear that receptor-like kinases （RLKs） and receptor-like proteins （RLPs） are key pattern-recognition receptors （PRRs） for microbe- and plant-derived molecular patterns that are associated with pathogen invasion. RLKs and RLPs involved in immune signaling belong to large gene families in plants and have undergone lineage specific expansion. Molecular evolution and population studies on phytopathogenic molecular signatures and their receptors have provided crucial insight into the co-evolution between plants and pathogens.
基金the Hi-Tech Research and Development Program of China (863) (2006AA10Z178 and 2006AA10A104)Knowledge Innovation Program of the Chinese Academy of Sciences
文摘Interactions between plants and microbes result in plant disease and symbiosis. The former causes considerable economic damage in modern agriculture, while the latter has produced great beneficial effects to our agriculture system. Comparison of the two interactions has revealed that a common panel of signaling pathways might participate in the establishment of the equilibrium between plant and microbes or its break-up. Plants appear to detect both pathogenic and symbiotic microbes by a similar set of genes. All symbiotic microbes seem to produce effectors to overcome plant basal defenses and it is speculated that symbiotic effectors have functions similar to pathogenic ones. Signaling molecules, salicylic acid （SA）, jasmonic acid （JA） and ethylene （ET）, are involved in both plant defense and symbiosis. Switching off signals contributing to deterioration of disease symptom would establish a new equilibrium between plant and pathogenic microbes. This would facilitate the development of strategies for durable disease resistance.
文摘Plants exploit several types of cell surface receptors for perception of extracellular signals, of which the extracellular leucine-rich repeat （eLRR）-containing receptors form the major class. Although the function of most plant eLRR receptors remains unclear, an increasing number of these receptors are shown to play roles in innate immunity and a wide variety of developmental processes. Recent efforts using domain swaps, gene shuffling analyses, site-directed mutagenesis, interaction studies, and crystallographic analyses resulted in the current knowledge on ligand binding and the mechanism of activation of plant eLRR receptors. This review provides an overview of eLRR receptor research, specificallysummarizing the recent understanding of interactions among plant eLRR receptors, their co-receptors and corresponding ligands. The functions of distinct eLRR receptor domains, and their role in structure, ligand perception and multimeric complex formation are discussed.
