Botrytis cinerea is one of the most destructive phytopathogenic fungi,causing significant losses to horticultural crops.As a necrotrophic fungus,B.cinerea obtains nutrients by killing host cells.Secreted cell death-in...Botrytis cinerea is one of the most destructive phytopathogenic fungi,causing significant losses to horticultural crops.As a necrotrophic fungus,B.cinerea obtains nutrients by killing host cells.Secreted cell death-inducing proteins(CDIPs)play a crucial role in necrotrophic infection;however,only a limited number have been reported.For highthroughput CDIP screening,we optimized the prokaryotic expression system and compared its efficiency with other commonly used protein expression systems.The optimized prokaryotic expression system showed superior effectiveness and efficiency and was selected for subsequent CDIP screening.The screening system verified fifty-five candidate proteins and identified two novel SGNH family CDIPs:BcRAE and BcFAT.BcRAE and BcFAT exhibited high expres-sion levels throughout the infection process.Site-directed mutagenesis targeting conserved Ser residues abolished the cell death-inducing activity of both BcRAE and BcFAT.Moreover,the transient expression of BcRAE and BcFAT in plants enhanced plant resistance against B.cinerea without inducing cell death,independent of their enzymatic activities.Our results suggest a high-efficiency screening system for high-throughput CDIP screening and provide new targets for further study of B.cinerea-plant interactions.展开更多
It has been almost three decades since the term ＂apoptosis＂ was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis ...It has been almost three decades since the term ＂apoptosis＂ was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis is an essential life process for metazoan animals and is critical for the formation and function of tissues and organs. In the adult mammalian body, apoptosis is especially important for proper functioning of the immune system. In recent years, along with the rapid advancement of molecular and cellular biology, great progress has been made in understanding the mechanisms leading to apoptosis. It is generally accepted that there are two major pathways ofapoptotic cell death induction： extrin- sic signaling through death receptors that leads to the formation of the death-inducing signaling complex （DISC）, and intrinsic signaling mainly through mitochondria which leads to the formation of the apoptosome. Formation of the DISC or apoptosome, respectively, activates initiator and common effector caspases that execute the apoptosis process. In the immune system, both pathways operate; however, it is not known whether they are sufficient to maintain lymphocyte homeostasis. Recently, new apoptotic mechanisms including caspase-independent pathways and granzyme-initiated pathways have been shown to exist in lymphocytes. This review will summarize our understanding of the mechanisms that control the homeostasis of various lymphocyte populations.展开更多
The expression of the cell death-inducing DNA fragmentation factorα-like effector（CIDE）family including Cidea,Cideb,and Cidec was significantly increased in mouse and human models of obesity.However,there was less ...The expression of the cell death-inducing DNA fragmentation factorα-like effector（CIDE）family including Cidea,Cideb,and Cidec was significantly increased in mouse and human models of obesity.However,there was less information on these genes’expression in pigs.Here,we hypothesized that different fat accumulation between lean（Duroc×Landrace×Yorkshire gilts,DLY）and obese（Lantang）pigs was attributed to porcine CIDE-modulating lipid metabolism.Our data showed that Cidea and Cidec were expressed at a high level in adipose tissue,and at a relatively high level in skeletal muscle,whereas Cideb was mainly expressed in the liver in both breeds of pig.Lantang pigs had higher white adipose and skeletal muscle Cidea and Cidec mR NA abundance,and hepatic and muscle Cideb mR NA than DLY pigs.Lipid metabolism-related genes including sterol regulatory element binding protein 1c（SREBP-1c）,hepatocyte nuclear factor-4α（HNF-4α）,peroxisome proliferator-activated receptorγcoactivator-1α（PGC-1α）,fatty acid synthase（FASN）,diacylglycerol O-acyltransferase 1（DGAT1）,and DGAT2 showed a higher expression level in adipose tissue from obese pigs than in that from lean pigs.Lantang pigs exhibited higher mR NA abundance for liver SREBP-1c,HNF-4α,and PGC-1α,and higher skeletal muscle SREBP-1c,HNF-4α,PGC-1α,and DGAT2 expression,as compared with DLY pigs.However,the perlipin2 mR NA levels in adipose tissues,liver,and skeletal muscle were significantly lower in obese pigs than in their lean counterparts.Furthermore,plasma non-esterified fatty acid（NEFA）,glucose,and triacylglycerol（TAG）levels were greater in obese pigs than in lean pigs.Finally,data from correlation analysis further found that CIDE mR NA expression was positively correlated with back fat thickness（BFT）,abdominal fat mass（AFM）,and the levels of NEFA,TAG,and glucose in the two breeds.Collectively,these data revealed that the porcine CIDEs possibly modulated lipid metabolism and contributed to the development of fat deposition and obesity in Lantang pigs.展开更多
Botrytis cinerea is a major necrotrophic pathogen responsible for significant crop losses worldwide.Alternative strategies to control B.cinerea are urgently needed to reduce dependence on chemical fungicides,which are...Botrytis cinerea is a major necrotrophic pathogen responsible for significant crop losses worldwide.Alternative strategies to control B.cinerea are urgently needed to reduce dependence on chemical fungicides,which are increasingly ineffective due to resistance and pose environmental risks.In this study,we identified two immunogenic epitopes derived from the B.cinerea cell death-inducing protein BcCrh1 and used them to engineer disease-resistant plants through a novel,spatially compartmentalized dual-epitope immune activation strategy.The first epitope is derived from a 35-amino acid intracellular peptide that exhibits both immunogenicity and cell death-inducing activity,which was mutated to separate these two properties.The second peptide represents an immunogenic portion of the protein that activates extracellular plant immunity.Transcriptomic and metabolomic analyses revealed that these epitopes trigger complementary defense pathways,and their co-expression integrates these responses into a robust,multilayered immunity,providing significantly enhanced protection compared with individual expression.Although constitutive expression of two epitopes conferred resistance,it also led to growth penalties.In contrast,pathogen-inducible expression of two epitopes preserved normal plant development while maintaining strong resistance to both B.cinerea and Pseudomonas syringae in Arabidopsis and tomato.This inducible strategy offers a major advantage by minimizing fitness costs while maximizing protection,highlighting the potential of spatially and temporally targeted epitope-based immune activation for durable and sustainable crop protection.展开更多
Recently,a work jointly studied by Ling Li and coworkers1 was published in Nature Materials,describing a reconfigurable DNA origami nanodevice designed to regulate CD95 death-inducing signaling of immune cells.The res...Recently,a work jointly studied by Ling Li and coworkers1 was published in Nature Materials,describing a reconfigurable DNA origami nanodevice designed to regulate CD95 death-inducing signaling of immune cells.The researchers utilized the DNA origami nanodevice to establish selective local immune tolerance and demonstrated its ability to alleviate rheumatoid arthritis(RA)in the inflamed synovial tissue of mice without causing any obvious side effects(Fig.1).This approach presents a novel idea for the development of drug interventions involving ligandreceptor interactions.展开更多
基金supported by the National Natural Science Foundation of China(31930086,U23A20264,31972475)the National Key R&D Program of China(2021YFD2100505).
文摘Botrytis cinerea is one of the most destructive phytopathogenic fungi,causing significant losses to horticultural crops.As a necrotrophic fungus,B.cinerea obtains nutrients by killing host cells.Secreted cell death-inducing proteins(CDIPs)play a crucial role in necrotrophic infection;however,only a limited number have been reported.For highthroughput CDIP screening,we optimized the prokaryotic expression system and compared its efficiency with other commonly used protein expression systems.The optimized prokaryotic expression system showed superior effectiveness and efficiency and was selected for subsequent CDIP screening.The screening system verified fifty-five candidate proteins and identified two novel SGNH family CDIPs:BcRAE and BcFAT.BcRAE and BcFAT exhibited high expres-sion levels throughout the infection process.Site-directed mutagenesis targeting conserved Ser residues abolished the cell death-inducing activity of both BcRAE and BcFAT.Moreover,the transient expression of BcRAE and BcFAT in plants enhanced plant resistance against B.cinerea without inducing cell death,independent of their enzymatic activities.Our results suggest a high-efficiency screening system for high-throughput CDIP screening and provide new targets for further study of B.cinerea-plant interactions.
文摘It has been almost three decades since the term ＂apoptosis＂ was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis is an essential life process for metazoan animals and is critical for the formation and function of tissues and organs. In the adult mammalian body, apoptosis is especially important for proper functioning of the immune system. In recent years, along with the rapid advancement of molecular and cellular biology, great progress has been made in understanding the mechanisms leading to apoptosis. It is generally accepted that there are two major pathways ofapoptotic cell death induction： extrin- sic signaling through death receptors that leads to the formation of the death-inducing signaling complex （DISC）, and intrinsic signaling mainly through mitochondria which leads to the formation of the apoptosome. Formation of the DISC or apoptosome, respectively, activates initiator and common effector caspases that execute the apoptosis process. In the immune system, both pathways operate; however, it is not known whether they are sufficient to maintain lymphocyte homeostasis. Recently, new apoptotic mechanisms including caspase-independent pathways and granzyme-initiated pathways have been shown to exist in lymphocytes. This review will summarize our understanding of the mechanisms that control the homeostasis of various lymphocyte populations.
基金supported by the National Natural Science Foundation of China(No.31402086)the China Agriculture Research System(CARS-36)+2 种基金the National Basic Research Program(973)of China(Nos.2013CB127301 and 2013CB127304)the Guangdong International Science and Technology Cooperation Program(No.2014A050503049)the Science and Technology Program of Guangdong Province(No.2016A020210041),China
文摘The expression of the cell death-inducing DNA fragmentation factorα-like effector（CIDE）family including Cidea,Cideb,and Cidec was significantly increased in mouse and human models of obesity.However,there was less information on these genes’expression in pigs.Here,we hypothesized that different fat accumulation between lean（Duroc×Landrace×Yorkshire gilts,DLY）and obese（Lantang）pigs was attributed to porcine CIDE-modulating lipid metabolism.Our data showed that Cidea and Cidec were expressed at a high level in adipose tissue,and at a relatively high level in skeletal muscle,whereas Cideb was mainly expressed in the liver in both breeds of pig.Lantang pigs had higher white adipose and skeletal muscle Cidea and Cidec mR NA abundance,and hepatic and muscle Cideb mR NA than DLY pigs.Lipid metabolism-related genes including sterol regulatory element binding protein 1c（SREBP-1c）,hepatocyte nuclear factor-4α（HNF-4α）,peroxisome proliferator-activated receptorγcoactivator-1α（PGC-1α）,fatty acid synthase（FASN）,diacylglycerol O-acyltransferase 1（DGAT1）,and DGAT2 showed a higher expression level in adipose tissue from obese pigs than in that from lean pigs.Lantang pigs exhibited higher mR NA abundance for liver SREBP-1c,HNF-4α,and PGC-1α,and higher skeletal muscle SREBP-1c,HNF-4α,PGC-1α,and DGAT2 expression,as compared with DLY pigs.However,the perlipin2 mR NA levels in adipose tissues,liver,and skeletal muscle were significantly lower in obese pigs than in their lean counterparts.Furthermore,plasma non-esterified fatty acid（NEFA）,glucose,and triacylglycerol（TAG）levels were greater in obese pigs than in lean pigs.Finally,data from correlation analysis further found that CIDE mR NA expression was positively correlated with back fat thickness（BFT）,abdominal fat mass（AFM）,and the levels of NEFA,TAG,and glucose in the two breeds.Collectively,these data revealed that the porcine CIDEs possibly modulated lipid metabolism and contributed to the development of fat deposition and obesity in Lantang pigs.
基金supported by the National Natural Science Foundation of China(grant no.32372514)the Research and Innovation Initiatives of WHPU(grant no.2024J02)+1 种基金Y.L.(202108280009)was funded by the China Scholarship Councilsupported by BARD(grant no.5261-20C)to A.S and T.M.
文摘Botrytis cinerea is a major necrotrophic pathogen responsible for significant crop losses worldwide.Alternative strategies to control B.cinerea are urgently needed to reduce dependence on chemical fungicides,which are increasingly ineffective due to resistance and pose environmental risks.In this study,we identified two immunogenic epitopes derived from the B.cinerea cell death-inducing protein BcCrh1 and used them to engineer disease-resistant plants through a novel,spatially compartmentalized dual-epitope immune activation strategy.The first epitope is derived from a 35-amino acid intracellular peptide that exhibits both immunogenicity and cell death-inducing activity,which was mutated to separate these two properties.The second peptide represents an immunogenic portion of the protein that activates extracellular plant immunity.Transcriptomic and metabolomic analyses revealed that these epitopes trigger complementary defense pathways,and their co-expression integrates these responses into a robust,multilayered immunity,providing significantly enhanced protection compared with individual expression.Although constitutive expression of two epitopes conferred resistance,it also led to growth penalties.In contrast,pathogen-inducible expression of two epitopes preserved normal plant development while maintaining strong resistance to both B.cinerea and Pseudomonas syringae in Arabidopsis and tomato.This inducible strategy offers a major advantage by minimizing fitness costs while maximizing protection,highlighting the potential of spatially and temporally targeted epitope-based immune activation for durable and sustainable crop protection.
基金support from the National Natural Science Foundation of China(82072087,31970893,32270976)funding by Science and Technology Projects in Guangzhou(202206010087,China).
文摘Recently,a work jointly studied by Ling Li and coworkers1 was published in Nature Materials,describing a reconfigurable DNA origami nanodevice designed to regulate CD95 death-inducing signaling of immune cells.The researchers utilized the DNA origami nanodevice to establish selective local immune tolerance and demonstrated its ability to alleviate rheumatoid arthritis(RA)in the inflamed synovial tissue of mice without causing any obvious side effects(Fig.1).This approach presents a novel idea for the development of drug interventions involving ligandreceptor interactions.
