Nanomaterials that can sequentially respond to internal and external stimuli,functioning as a sequential gate,have great potential for targeting different aspects of antitumor immunity.Herein,we construct a mannose-mo...Nanomaterials that can sequentially respond to internal and external stimuli,functioning as a sequential gate,have great potential for targeting different aspects of antitumor immunity.Herein,we construct a mannose-modified,pH and reactive oxygen species(ROS) sequential-responsive,transformable dualimmunofunction nanoprodrug(MpRTNP).This nanoprodrug encapsulates a transforming growth factor-β(TGF-β) receptor inhibitor SD-208(MpRTNP@SD),to simultaneously alleviate the immunosuppressive effects of TGF-β and tumor-associated macrophages(TAMs).In the weakly acidic tumor microenvironment(TME),the vesicle-micelle morphology transformation occurs owing to the protonation of PC7A,which is accompanied by SD-208 release to inhibit cancer-associated fibroblasts and regulatory T cells.The transformed micelles then target TAMs via mannose receptor-media ted endocytosis.Upon laser irradiation,the thioketal linker is cleaved,releasing conjugated chlorin e6 and generating ROS,which facilitates TAM polarization.The PC7A^(+) segment activates the stimulator of the interferon gene in TAMs with elevated phosphorylation of TANK binding kinase 1 and interferon regulatory factor 3,and type I interferon secretion.MpRTNP@SD displays superior abscopal effects and robust antitumor immunity,as evidenced by increased CD8^(+)/CD4^(+) T cell infiltration and reduced regulatory T cell(Treg) ratios.Mouse survival time is prolonged after combination with the CD47 antibody.This study provides a novel strategy for potent antitumor immunotherapy through pH and ROS sequential-gated spatiotemporal regulation of the TME.展开更多
Innate immunity is critical for the control of virus infection and operates to restrict viral susceptibility and direct antiviral immunity for protection from acute or chronic viral-associated diseases including cance...Innate immunity is critical for the control of virus infection and operates to restrict viral susceptibility and direct antiviral immunity for protection from acute or chronic viral-associated diseases including cancer. RIG-I like receptors(RLRs) are cytosolic RNA helicases that function as pathogen recognition receptors to detect RNA pathogen associated molecular patterns(PAMPs) of virus infection. The RLRs include RIG-I, MDA5, and LGP2. They function to recognize and bind to PAMP motifs within viral RNA in a process that directs the RLR to trigger downstream signaling cascades that induce innate immunity that controls viral replication and spread. Products of RLR signaling also serve to modulate the adaptive immune response to infection. Recent studies have additionally connected RLRs to signaling cascades that impart inflammatory and apoptotic responses to virus infection. Viral evasion of RLR signaling supports viral outgrowth and pathogenesis, including the onset of viral-associated cancer.展开更多
The Lome Infection and Immunity Conference is one of five scientific meetings held during each month of February at the Cumberland resort in the picturesque seaside town of Lome,on the Great Ocean Road in Victoria(Aus...The Lome Infection and Immunity Conference is one of five scientific meetings held during each month of February at the Cumberland resort in the picturesque seaside town of Lome,on the Great Ocean Road in Victoria(Australia).The specific aim of the meeting is to bring together basic,clinical and translational researchers-those who examine microbes and their impact on the innate or adaptive immune response,researchers who study the mechanisms that regulate immune responses,and those who apply this knowledge to preventing and treating infectious and in”ammatory diseases.The average number of attendees is 220,with registrants appreciative of the welcoming and relaxed atmosphere(Fig.1).展开更多
Objective:Trained immunity of natural killer(NK)cells has shown great potential in the treatment of cancers by eliciting enhanced effector responses to restimulation by cytokines or cancer cells for long time periods ...Objective:Trained immunity of natural killer(NK)cells has shown great potential in the treatment of cancers by eliciting enhanced effector responses to restimulation by cytokines or cancer cells for long time periods after preactivation.However,the human NK cells responsible for the generation and maintenance of trained immunity are largely unknown.We hypothesized that heterogeneous human NK cells would respond differentially to stimulation with a combination of IL-12,IL-15,and IL-18,and that an NK cell subset might exist that is mainly responsible for the induction of trained immunity.On the basis of our hypothesis,we aimed to identify the subset from which cytokine-trained human NK cells originate and to explore possible regulatory targets for drug intervention.Methods:Flow cytometry assays were performed to analyze the functions of cytokine-trained NK cells and examine cell division and protein expression in NK cell subsets.Single-cell RNA sequencing(scRNA-seq)plus TotalSeq™technology was used to track the heterogeneity of NK cells during the induction of trained immunity.Results:Traditional developmental markers for peripheral NK cells were unable to identify the precursors of human NK cells with trained immunity.Therefore,we used scRNA-seq plus TotalSeq™technology to track the heterogeneity of NK cells during the induction of trained immunity and identified a unique cluster of CD57−NKG2A+EZH2+IFNG+MKI67+IL12R+IL15R+IL18R+NK cells.Enrichment and pseudotime trajectory analyses suggested that this cluster of NK cells contained the precursor of trained NK cells.We then used flow cytometry to further investigate the role of EZH2 in trained NK precursors and found that CD57−NKG2A+EZH2+NK cells had faster cell cycles and an enhanced trained phenotype,and EZH2 inhibition significantly impaired the induction of trained immunity in NK cells.These results suggested that EZH2 is a unique epigenetic marker of precursors of human NK cells with trained immunity.Conclusions:Our work revealed human NK heterogeneity in the induction of trained immunity,identified the precursor subset for trained NK cells,and demonstrated the critical role of EZH2 in the induction of trained immunity in human NK cells.展开更多
Severe Acute Respiratory Syndrome （SARS） is a deadly infectious disease caused by SARS Coronavirus （SARS-CoV）. Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvan...Severe Acute Respiratory Syndrome （SARS） is a deadly infectious disease caused by SARS Coronavirus （SARS-CoV）. Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are alw needed more urgently in a pandemic. The development of a safe and effective mucosal adjuvant and vaccine ays for prevention of emergent infectious diseases such as SARS will be an important advancement. PIKA, a stabilized derivative of Poly （I：C）, was previously reported to be safe and potent as adjuvant in mouse models. In the present study, we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly （I：C） derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus. Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites, co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity. When intranasal immunization was used, PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response. Overall, PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.展开更多
INTRODUCTION An effective coordination of immune and non-immune cells is essential for generating optimal regional immunity to combat tumorigenesis and infection at barrier tissues such as lung.Regional immune structu...INTRODUCTION An effective coordination of immune and non-immune cells is essential for generating optimal regional immunity to combat tumorigenesis and infection at barrier tissues such as lung.Regional immune structures such as inducible bronchus-associated lymphoid tissue(iBALT)and tertiary lymphoid structure(TLS)play essential roles in modulating lung local immune responses.While the identification of iBALTs or TLS is generally dependent on conventional histology,it remains poorly understood how immune cells are spatiotemporally coordinated in the lung at single-cell resolution to effectively eliminate malignant cells and invading pathogens.Recently studies have revealed the presence of dendritic cell(DC)-T immunity hubs in human lung with close association with tumor immunotherapy response[1],antiviral immunity[2],and inflammation resolution[3].展开更多
In nature,plants are under attack by a range of pathogens.To cope with these pathogens,plants have evolved a sophisticated immune system,including pattern-triggered immunity(PTI)initiated by pattern recognition recept...In nature,plants are under attack by a range of pathogens.To cope with these pathogens,plants have evolved a sophisticated immune system,including pattern-triggered immunity(PTI)initiated by pattern recognition receptors on the cell surface and effector-triggered immunity(ETI)activated by intracellular nucleotide-binding and leucine-rich repeat receptors.In recent years,increasing evidence has demonstrated that organelles such as the chloroplast play crucial roles in complete activation of plant immunity.In this review,we focus on the chloroplast and summarize its role in regulating the activation of immune events,including influx of calcium(Ca^(2+)),accumulation of reactive oxygen species(ROS),biosynthesis of phytohormones,and expression of defense-related genes.Because information exchange between the chloroplast and the nucleus is very important during plant immunity,we also highlight the importance of chloroplast-nucleus communication via stromules in plant immunity.This review reveals the function of the chloroplast in maintaining the trade-off between plant growth and immunity,and expands our understanding of how chloroplasts enable complete activation of plant immunity.展开更多
In their natural habitats,bacteria thrive in densely populated environments(such as soil and the human gut)and compete with other microorganisms for ecological niches[1].Secretion systems enable bacteria to export pro...In their natural habitats,bacteria thrive in densely populated environments(such as soil and the human gut)and compete with other microorganisms for ecological niches[1].Secretion systems enable bacteria to export proteins into their surroundings and play key roles in interbacterial competition,development,nutrient acquisition,and virulence[2–4].Type VII secretion system b(T7SSb)has been primarily identified in low-G+C Firmicutes,which exhibit significant inter-and intraspecies heterogeneity in secreting putative toxin effectors.展开更多
Prof.Zhijian James Chen,a distinguished scientist in the field of innate immunity,has been honored with the 2025 Paul Ehrlich and Ludwig Darmstaedter Prize and the 2024 Albert Lasker Basic Medical Research Award for h...Prof.Zhijian James Chen,a distinguished scientist in the field of innate immunity,has been honored with the 2025 Paul Ehrlich and Ludwig Darmstaedter Prize and the 2024 Albert Lasker Basic Medical Research Award for his groundbreaking discovery of the enzyme cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS).His research has transformed the understanding of innate immune responses,particularly the role of cGAS as a cytosolic DNA sensor that triggers an interferon response.In this dialogue,Prof.Chen reflects on his research journey,from his initial exploration of ubiquitin and nuclear factor-kB(NF-kB)signaling to his discoveries of mitochondrial antiviral-signaling protein(MAVS)and cGAS,highlighting his lifelong interest in cell signaling and human diseases.The interview underscores the importance of perseverance and the pursuit of impactful research questions in scientific endeavors.This scholarly exchange offers a mentor-like perspective for aspiring scientists,encapsulating the essence of a successful career in biomedical research.展开更多
Lipid droplets(LDs)are intracellular organelles that can be induced and interact with phagosomes during the process of pathogen phagocytosis in macrophages.However,the function of LDs in phagocytosis remains elusive.H...Lipid droplets(LDs)are intracellular organelles that can be induced and interact with phagosomes during the process of pathogen phagocytosis in macrophages.However,the function of LDs in phagocytosis remains elusive.Here,we unveil the role of LDs in modulating phagosome formation via a fungal infection model.Specifically,LD accumulation restricted the degree of phagosome formation and protected macrophages from death.Mechanistically,LD formation competitively consumed the intracellular endoplasmic reticulum membrane and altered RAC1 translocation and GTPase activity,which resulted in limited phagosome formation in macrophages during fungal engulfment.Mice with Hilpda-deficient macrophages were more susceptible to the lethal sequelae of systemic infection with C.albicans.Notably,administration of the ATGL inhibitor atglistatin improved host outcomes in disseminated fungal infections.Taken together,our study elucidates the mechanism by which LDs control phagosome formation to prevent immune cell death and offers a potential drug target for the treatment of C.albicans infections.展开更多
Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this conditi...Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this condition,reported by our team and others,are very limited worldwide.As such,our current knowledge of this new disease remains preliminary.This review aims to provide a brief overview of the clinical manifestations,pathogenesis,and treatment strategies for this novel IEI.Data sources A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency.Our search strategy was“ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor”as of the time of manuscript submission.Results The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer,abdominal pain,and diarrhea in pediatric males.In some cases,immunodeficiency and autoimmunity can also be prominent.Targeted Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene.Western blotting for ELF4 expression of the patient’s cells can confirm the pathogenic effect of the variant.To fully confirm the pathogenicity of the variant,further functional test is strongly advised.Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder.Conclusions Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX.When atypical presentations are prominent,variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function.Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.展开更多
The immune system plays a crucial role in protecting the body from invading pathogens and maintaining tissue homoeostasis.Maintaining homoeostatic lipid metabolism is an important aspect of efficient immune cell funct...The immune system plays a crucial role in protecting the body from invading pathogens and maintaining tissue homoeostasis.Maintaining homoeostatic lipid metabolism is an important aspect of efficient immune cell function and when disrupted immune cell function is impaired.There are numerous metabolic diseases whereby systemic lipid metabolism and cellular function is impaired.In the context of metabolic disorders,chronic inflammation is suggested to be a major contributor to disease progression.A major contributor to tissue dysfunction in metabolic disease is ectopic lipid deposition,which is generally caused by diet and genetic factors.Thus,we propose the idea,that similar to tissue and organ damage in metabolic disorders,excessive accumulation of lipid in immune cells promotes a dysfunctional immune system(beyond the classical foam cell)and contributes to disease pathology.Herein,we review the evidence that lipid accumulation through diet can modulate the production and function of immune cells by altering cellular lipid content.This can impact immune cell signalling,activation,migration,and death,ultimately affecting key aspects of the immune system such as neutralising pathogens,antigen presentation,effector cell activation and resolving inflammation.展开更多
Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against infection.The cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains elusive.Eos...Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against infection.The cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains elusive.Eosinophils can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune defense.Here we report that eosinophils are required for the generation of memory CD8+T cells by inhibiting CD8+T cell apoptosis.Eosinophil-deficient mice display significantly impaired memory CD8+T cell response and weakened resistance against Listeria monocytogenes(L.m.)infection.Mechanistically,eosinophils secrete interleukin-4(IL-4)to inhibit JNK/Caspase-3 dependent apoptosis of CD8+T cells upon L.m.infection in vitro.Furthermore,active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+T cell apoptosis during early stage of L.m.infection in vivo.Adoptive transfer of wild-type(WT)eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+T cell memory responses.Together,our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+T cell memory and enhances immune defense against L.m.infection.Our study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.展开更多
Background:Despite significant strides in lung cancer immunotherapy,the response rates for Kirsten rat sarcoma viral oncogene homolog(KRAS)-driven lung adenocarcinoma(LUAD)patients remain limited.Fibrinogen-like prote...Background:Despite significant strides in lung cancer immunotherapy,the response rates for Kirsten rat sarcoma viral oncogene homolog(KRAS)-driven lung adenocarcinoma(LUAD)patients remain limited.Fibrinogen-like protein 1(FGL1)is a newly identified immune checkpoint target,and the study of related resistance mechanisms is crucial for improving the treatment outcomes of LUAD patients.This study aimed to elucidate the potential mechanism by which FGL1 regulates the tumor microenvironment in KRAS-mutated cancer.Methods:The expression levels of FGL1 and SET1 histone methyltransferase(SET1A)in lung cancer were assessed using public databases and clinical sam-ples.Lentiviruses were constructed for transduction to overexpress or silence FGL1 in lung cancer cells and mouse models.The effects of FGL1 and Yes-associated protein(Yap)on the immunoreactivity of cytotoxic T cells in tumor tissues were evaluated using immunofluorescence staining and flow cytometry.Chromatin immunoprecipitation and dual luciferase reporter assays were used to study the SET1A-directed transcriptional program.Results:Upregulation of FGL1 expression in KRAS-mutated cancer was inversely correlated with the infiltration of CD8^(+)T cells.Mechanistically,KRAS activated extracellular signal-regulated kinase 1/2(ERK1/2),which subsequently phosphorylated SET1A and increased its stability and nuclear localization.SET1A-mediated methylation of Yap led to Yap sequestration in the nucleus,thereby promoting Yap-induced transcription of FGL1 and immune evasion in KRAS-driven LUAD.Notably,dual blockade of programmed cell death-1(PD-1)and FGL1 further increased the therapeutic efficacy of anti-PD-1 immunotherapy in LUAD patients.Conclusion:FGL1 could be used as a diagnostic biomarker of KRAS-mutated lung cancer,and targeting the Yap-FGL1 axis could increase the efficacy of anti-PD-1 immunotherapy.展开更多
CD8^(+)T cell immune responses are regulated by multi-layer networks,while the post-translational regulation remains largely unknown.Transmembrane ectodomain shedding is an important post-translational process orchest...CD8^(+)T cell immune responses are regulated by multi-layer networks,while the post-translational regulation remains largely unknown.Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins.Here,by targeting the sheddase A Disintegrin and Metalloprotease(ADAM)17,we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8^(+)T cells.Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8^(+)T cells.T cellspecific deletion of ADAM17 led to a dramatic increase in effector CD8^(+)T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors.Mechanistically,ADAM17 regulated CD8^(+)T cells through cleavage of membrane CD122.ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8^(+)T cells.Intriguingly,inhibition of ADAM17 in CD8^(+)T cells improved the efficacy of chimeric antigen receptor(CAR)T cells in solid tumors.Our findings reveal a critical post-translational regulation in CD8^(+)T cells,providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.展开更多
Plants need to fine-tune defense responses to maintain a robust but flexible host barrier to various pathogens.Helix-loop-helix/basic helix-loop-helix(HLH/bHLH)complexes play important roles in fine-tuning plant devel...Plants need to fine-tune defense responses to maintain a robust but flexible host barrier to various pathogens.Helix-loop-helix/basic helix-loop-helix(HLH/bHLH)complexes play important roles in fine-tuning plant development.However,the function of these genes in plant immunity and how they are regulated remain obscure.Here,we identified an atypical bHLH transcription factor,Oryza sativa(Os)HLH46,that interacts with rice receptor-like cytoplasmic kinase(RLCK)Os BRASSINOSTEROID-SIGNALING KINASE1-2(OsBSK1-2),which plays a key role in rice blast resistance.OsBSK1-2 stabilized OsHLH46 both in vivo and in vitro.In addition,OsHLH46 positively regulates rice blast resistance,which depends on OsBSK1-2.OsHLH46 has no transcriptional activation activity and interacts with a typical bHLH protein,OsbHLH6,which negatively regulates rice blast resistance.OsbHLH6 binds to the promoter of OsWRKY45 and inhibits its expression,while OsHLH46 suppresses the function of OsbHLH6 by blocking its DNA binding and transcriptional inhibition of OsWRKY45.Consistent with these findings,OsWRKY45 was up-regulated in OsHLH46-overexpressing plants.In addition,the oshlh46 mutant overexpressing OsbHLH6 is more susceptible to Magnaporthe oryzae than is the wild type,suggesting that OsHLH46 suppresses OsbHLH6-mediated rice blast resistance.Our results not only demonstrated that OsBSK1-2 regulates rice blast resistance via the OsHLH46/OsbHLH6 complex,but also uncovered a new mechanism for plants to fine-tune plant immunity by regulating the HLH/bHLH complex via RLCKs.展开更多
Inborn errors of the signal transducer and activator of transcription 1(STAT1)result in four types of immunodeficiency disease with varying degrees of impaired STAT1 function:autosomal recessive(AR)complete STAT1 defi...Inborn errors of the signal transducer and activator of transcription 1(STAT1)result in four types of immunodeficiency disease with varying degrees of impaired STAT1 function:autosomal recessive(AR)complete STAT1 deficiency,AR partial STAT1 deficiency,autosomal dominant(AD)STAT1 deficiency,and AD STAT1 gain-of-function(STAT1-GOF).Of which,the STAT1-GOF mutations promote a clinical syndrome of immune dysregulation characterized by recurrent infections,especially chronic mucocutaneous candidiasis(CMC)and Talaromyces marneffei infection and predisposition to humoral autoimmunity.STAT1-GOF mutations lead to enhanced phosphorylation of STAT1(pSTAT1),delayed dephosphorylation,and impaired nuclear dephosphorylation.As a result,the development of T helper(Th)17 cells is impaired,limiting the production of interleukin(IL)-17,which plays an important role in antifungal immunity.Additionally,mutations can also cause a decrease in the proportion of CD4^(+),CD8^(+),and natural killer(NK)cells.Recent research demonstrated that in the absence of overt infection,STAT-GOF mice can disrupt naïve CD4^(+)T cell homeostasis and promote expansion and differentiation of abnormal T-follicular helper/T-helper 1-like(Tfh/Th1-like)T cells and germinal center-like(GC-like)B cells,and thus reminds us of the complex molecular mechanism of autoimmune disease with/without fungal infection,which may further involve specific clinical treatment including antifungal and anti-autoimmunity therapies.In addition,sex and location of mutation were also associated with the clinical phenotype.Individuals with DNA binding domain(DBD)mutations had a higher prevalence of autoimmunity and aberrant B cell activation.Disrupted CD4^(+)T cell homeostasis occurred sooner and more robustly in females,highlighting the importance of specific treatment to normalize STAT1 expression and restore immune tolerance in patients with STAT1-GOF syndrome.Herein,we provide a comprehensive review of STAT1-GOF aiming to further clarify the regulatory mechanism of cellular and humoral immune deficiency in patients with fungal infection with or without autoimmunity.展开更多
While conventional chemical fungicides directly eliminate pathogens,plant immunity inducers activate or prime plant immunity.In recent years,considerable progress has been made in understanding the mechanisms of immun...While conventional chemical fungicides directly eliminate pathogens,plant immunity inducers activate or prime plant immunity.In recent years,considerable progress has been made in understanding the mechanisms of immune regulation in plants.The development and application of plant immunity inducers based on the principles of plant immunity represent a new field in plant protection research.In this review,we describe the mechanisms of plant immunity inducers in terms of plant immune system activation,summarize the various classes of reported plant immunity inducers(proteins,oligosaccharides,chemicals,and lipids),and review methods for the identification or synthesis of plant immunity inducers.The current situation,new strategies,and future prospects in the development and application of plant immunity inducers are also discussed.展开更多
基金supported by National Natural Science Foundation of China(Nos.52103190 and 52103191)Special Program for Supporting Innovative Youth Talent Teams(No.32320683)+1 种基金Start-up Grant(Nos.32340311 and 35220151) from Zhengzhou UniversityNatural Science Foundation of Henan Province(No.242300420127)。
文摘Nanomaterials that can sequentially respond to internal and external stimuli,functioning as a sequential gate,have great potential for targeting different aspects of antitumor immunity.Herein,we construct a mannose-modified,pH and reactive oxygen species(ROS) sequential-responsive,transformable dualimmunofunction nanoprodrug(MpRTNP).This nanoprodrug encapsulates a transforming growth factor-β(TGF-β) receptor inhibitor SD-208(MpRTNP@SD),to simultaneously alleviate the immunosuppressive effects of TGF-β and tumor-associated macrophages(TAMs).In the weakly acidic tumor microenvironment(TME),the vesicle-micelle morphology transformation occurs owing to the protonation of PC7A,which is accompanied by SD-208 release to inhibit cancer-associated fibroblasts and regulatory T cells.The transformed micelles then target TAMs via mannose receptor-media ted endocytosis.Upon laser irradiation,the thioketal linker is cleaved,releasing conjugated chlorin e6 and generating ROS,which facilitates TAM polarization.The PC7A^(+) segment activates the stimulator of the interferon gene in TAMs with elevated phosphorylation of TANK binding kinase 1 and interferon regulatory factor 3,and type I interferon secretion.MpRTNP@SD displays superior abscopal effects and robust antitumor immunity,as evidenced by increased CD8^(+)/CD4^(+) T cell infiltration and reduced regulatory T cell(Treg) ratios.Mouse survival time is prolonged after combination with the CD47 antibody.This study provides a novel strategy for potent antitumor immunotherapy through pH and ROS sequential-gated spatiotemporal regulation of the TME.
基金supported by National Institutes of Health grants AI083019, AI104002, and AI88778
文摘Innate immunity is critical for the control of virus infection and operates to restrict viral susceptibility and direct antiviral immunity for protection from acute or chronic viral-associated diseases including cancer. RIG-I like receptors(RLRs) are cytosolic RNA helicases that function as pathogen recognition receptors to detect RNA pathogen associated molecular patterns(PAMPs) of virus infection. The RLRs include RIG-I, MDA5, and LGP2. They function to recognize and bind to PAMP motifs within viral RNA in a process that directs the RLR to trigger downstream signaling cascades that induce innate immunity that controls viral replication and spread. Products of RLR signaling also serve to modulate the adaptive immune response to infection. Recent studies have additionally connected RLRs to signaling cascades that impart inflammatory and apoptotic responses to virus infection. Viral evasion of RLR signaling supports viral outgrowth and pathogenesis, including the onset of viral-associated cancer.
文摘The Lome Infection and Immunity Conference is one of five scientific meetings held during each month of February at the Cumberland resort in the picturesque seaside town of Lome,on the Great Ocean Road in Victoria(Australia).The specific aim of the meeting is to bring together basic,clinical and translational researchers-those who examine microbes and their impact on the innate or adaptive immune response,researchers who study the mechanisms that regulate immune responses,and those who apply this knowledge to preventing and treating infectious and in”ammatory diseases.The average number of attendees is 220,with registrants appreciative of the welcoming and relaxed atmosphere(Fig.1).
基金This work was supported by grants from The National Key R&D Program(Grant Nos.2018YFC1313400,2018YFC1313000,and 2018YFC1313002)The National Natural Science Foundation of China(Grant Nos.81872166,U20A20375,31600705,81974416,and 81702405)The Tianjin Natural Science Foundation(Grant No.17JCQNJC09000)。
文摘Objective:Trained immunity of natural killer(NK)cells has shown great potential in the treatment of cancers by eliciting enhanced effector responses to restimulation by cytokines or cancer cells for long time periods after preactivation.However,the human NK cells responsible for the generation and maintenance of trained immunity are largely unknown.We hypothesized that heterogeneous human NK cells would respond differentially to stimulation with a combination of IL-12,IL-15,and IL-18,and that an NK cell subset might exist that is mainly responsible for the induction of trained immunity.On the basis of our hypothesis,we aimed to identify the subset from which cytokine-trained human NK cells originate and to explore possible regulatory targets for drug intervention.Methods:Flow cytometry assays were performed to analyze the functions of cytokine-trained NK cells and examine cell division and protein expression in NK cell subsets.Single-cell RNA sequencing(scRNA-seq)plus TotalSeq™technology was used to track the heterogeneity of NK cells during the induction of trained immunity.Results:Traditional developmental markers for peripheral NK cells were unable to identify the precursors of human NK cells with trained immunity.Therefore,we used scRNA-seq plus TotalSeq™technology to track the heterogeneity of NK cells during the induction of trained immunity and identified a unique cluster of CD57−NKG2A+EZH2+IFNG+MKI67+IL12R+IL15R+IL18R+NK cells.Enrichment and pseudotime trajectory analyses suggested that this cluster of NK cells contained the precursor of trained NK cells.We then used flow cytometry to further investigate the role of EZH2 in trained NK precursors and found that CD57−NKG2A+EZH2+NK cells had faster cell cycles and an enhanced trained phenotype,and EZH2 inhibition significantly impaired the induction of trained immunity in NK cells.These results suggested that EZH2 is a unique epigenetic marker of precursors of human NK cells with trained immunity.Conclusions:Our work revealed human NK heterogeneity in the induction of trained immunity,identified the precursor subset for trained NK cells,and demonstrated the critical role of EZH2 in the induction of trained immunity in human NK cells.
基金supported by the National Natural Science Foundation of China (30670097)National Basic Research Program of China (973 Program) (2005CB522903)+1 种基金National Key R&D Program (2007BAI28B04)National S&T Major Project on Major Infectious Diseases (2008ZX10001-010)from the Ministry of Science and Technology of the People’s Republic of China
文摘Severe Acute Respiratory Syndrome （SARS） is a deadly infectious disease caused by SARS Coronavirus （SARS-CoV）. Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are alw needed more urgently in a pandemic. The development of a safe and effective mucosal adjuvant and vaccine ays for prevention of emergent infectious diseases such as SARS will be an important advancement. PIKA, a stabilized derivative of Poly （I：C）, was previously reported to be safe and potent as adjuvant in mouse models. In the present study, we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly （I：C） derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus. Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites, co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity. When intranasal immunization was used, PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response. Overall, PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.
基金supported by Grants from the National Key R&D Program of China(2023YFA1801400)National Natural Science Foundation of China(92374115 and 82388201).
文摘INTRODUCTION An effective coordination of immune and non-immune cells is essential for generating optimal regional immunity to combat tumorigenesis and infection at barrier tissues such as lung.Regional immune structures such as inducible bronchus-associated lymphoid tissue(iBALT)and tertiary lymphoid structure(TLS)play essential roles in modulating lung local immune responses.While the identification of iBALTs or TLS is generally dependent on conventional histology,it remains poorly understood how immune cells are spatiotemporally coordinated in the lung at single-cell resolution to effectively eliminate malignant cells and invading pathogens.Recently studies have revealed the presence of dendritic cell(DC)-T immunity hubs in human lung with close association with tumor immunotherapy response[1],antiviral immunity[2],and inflammation resolution[3].
基金supported by grants from the Natural Science Foundation of Fujian Province,China(grant no.2024J09022)the National Natural Science Foundation of China(grant no.32370302)the Open Fund of Fujian Provincial Key Laboratory of Eco-Industrial Green Technology(grant no.WYKF-EIGT2022-6).
文摘In nature,plants are under attack by a range of pathogens.To cope with these pathogens,plants have evolved a sophisticated immune system,including pattern-triggered immunity(PTI)initiated by pattern recognition receptors on the cell surface and effector-triggered immunity(ETI)activated by intracellular nucleotide-binding and leucine-rich repeat receptors.In recent years,increasing evidence has demonstrated that organelles such as the chloroplast play crucial roles in complete activation of plant immunity.In this review,we focus on the chloroplast and summarize its role in regulating the activation of immune events,including influx of calcium(Ca^(2+)),accumulation of reactive oxygen species(ROS),biosynthesis of phytohormones,and expression of defense-related genes.Because information exchange between the chloroplast and the nucleus is very important during plant immunity,we also highlight the importance of chloroplast-nucleus communication via stromules in plant immunity.This review reveals the function of the chloroplast in maintaining the trade-off between plant growth and immunity,and expands our understanding of how chloroplasts enable complete activation of plant immunity.
基金supported by the National Natural Science Foundation of China(82225028,82172287,32171265,31900879,and 32370185)the National Key Research and Development Program of China(2021YFC2301403)+1 种基金the high-level personnel introduction grant form Fujian Normal University(Z0210509)the Natural Science Foundation of Fujian Province(2023J011797 and 2024J010025).
文摘In their natural habitats,bacteria thrive in densely populated environments(such as soil and the human gut)and compete with other microorganisms for ecological niches[1].Secretion systems enable bacteria to export proteins into their surroundings and play key roles in interbacterial competition,development,nutrient acquisition,and virulence[2–4].Type VII secretion system b(T7SSb)has been primarily identified in low-G+C Firmicutes,which exhibit significant inter-and intraspecies heterogeneity in secreting putative toxin effectors.
文摘Prof.Zhijian James Chen,a distinguished scientist in the field of innate immunity,has been honored with the 2025 Paul Ehrlich and Ludwig Darmstaedter Prize and the 2024 Albert Lasker Basic Medical Research Award for his groundbreaking discovery of the enzyme cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS).His research has transformed the understanding of innate immune responses,particularly the role of cGAS as a cytosolic DNA sensor that triggers an interferon response.In this dialogue,Prof.Chen reflects on his research journey,from his initial exploration of ubiquitin and nuclear factor-kB(NF-kB)signaling to his discoveries of mitochondrial antiviral-signaling protein(MAVS)and cGAS,highlighting his lifelong interest in cell signaling and human diseases.The interview underscores the importance of perseverance and the pursuit of impactful research questions in scientific endeavors.This scholarly exchange offers a mentor-like perspective for aspiring scientists,encapsulating the essence of a successful career in biomedical research.
基金supported by grants from the National Natural Science Foundation of China(82321002,32230033 and 81930039 to CG)the National Key Research and Development Program of China(2021YFC2300603 and 2023YFC2306102 to CG)supported by the Future Scholar Program of Shandong University(21510082364125).
文摘Lipid droplets(LDs)are intracellular organelles that can be induced and interact with phagosomes during the process of pathogen phagocytosis in macrophages.However,the function of LDs in phagocytosis remains elusive.Here,we unveil the role of LDs in modulating phagosome formation via a fungal infection model.Specifically,LD accumulation restricted the degree of phagosome formation and protected macrophages from death.Mechanistically,LD formation competitively consumed the intracellular endoplasmic reticulum membrane and altered RAC1 translocation and GTPase activity,which resulted in limited phagosome formation in macrophages during fungal engulfment.Mice with Hilpda-deficient macrophages were more susceptible to the lethal sequelae of systemic infection with C.albicans.Notably,administration of the ATGL inhibitor atglistatin improved host outcomes in disseminated fungal infections.Taken together,our study elucidates the mechanism by which LDs control phagosome formation to prevent immune cell death and offers a potential drug target for the treatment of C.albicans infections.
基金funded by National Natural Science Foundation of China(82101908,82371823)Postdoc Fund of Chongqing Natural Science Foundation(cstc2021jcyj-bshX0226).
文摘Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this condition,reported by our team and others,are very limited worldwide.As such,our current knowledge of this new disease remains preliminary.This review aims to provide a brief overview of the clinical manifestations,pathogenesis,and treatment strategies for this novel IEI.Data sources A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency.Our search strategy was“ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor”as of the time of manuscript submission.Results The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer,abdominal pain,and diarrhea in pediatric males.In some cases,immunodeficiency and autoimmunity can also be prominent.Targeted Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene.Western blotting for ELF4 expression of the patient’s cells can confirm the pathogenic effect of the variant.To fully confirm the pathogenicity of the variant,further functional test is strongly advised.Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder.Conclusions Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX.When atypical presentations are prominent,variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function.Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.
基金National Health and Medical Research Council of Australia grants GNT2027074&GNT2012119 to KM,GNT1189012 to GIL and GNT1194329 to AJM.
文摘The immune system plays a crucial role in protecting the body from invading pathogens and maintaining tissue homoeostasis.Maintaining homoeostatic lipid metabolism is an important aspect of efficient immune cell function and when disrupted immune cell function is impaired.There are numerous metabolic diseases whereby systemic lipid metabolism and cellular function is impaired.In the context of metabolic disorders,chronic inflammation is suggested to be a major contributor to disease progression.A major contributor to tissue dysfunction in metabolic disease is ectopic lipid deposition,which is generally caused by diet and genetic factors.Thus,we propose the idea,that similar to tissue and organ damage in metabolic disorders,excessive accumulation of lipid in immune cells promotes a dysfunctional immune system(beyond the classical foam cell)and contributes to disease pathology.Herein,we review the evidence that lipid accumulation through diet can modulate the production and function of immune cells by altering cellular lipid content.This can impact immune cell signalling,activation,migration,and death,ultimately affecting key aspects of the immune system such as neutralising pathogens,antigen presentation,effector cell activation and resolving inflammation.
基金supported by grants from the National Key R&D Program(2018YFA0507401)National Natural Science Foundation of China(82388201)CAMS Innovation Fund for Medical Sciences(2021-I2M-1-017).
文摘Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against infection.The cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains elusive.Eosinophils can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune defense.Here we report that eosinophils are required for the generation of memory CD8+T cells by inhibiting CD8+T cell apoptosis.Eosinophil-deficient mice display significantly impaired memory CD8+T cell response and weakened resistance against Listeria monocytogenes(L.m.)infection.Mechanistically,eosinophils secrete interleukin-4(IL-4)to inhibit JNK/Caspase-3 dependent apoptosis of CD8+T cells upon L.m.infection in vitro.Furthermore,active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+T cell apoptosis during early stage of L.m.infection in vivo.Adoptive transfer of wild-type(WT)eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+T cell memory responses.Together,our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+T cell memory and enhances immune defense against L.m.infection.Our study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.
基金supported by National Natural Science Foundation of China Youth Project 82002450(to H.Q.)The Research Program for Higher Education Institutions in Anhui Province 2022AH030081(to S.Z.)+1 种基金Basic and Clinical Collaboration Enhancement Program of Anhui Medical University 2020xkjT023(to H.Q.)The Research Program for Higher Education Institutions in Anhui Province 2023AH050656(to H.Q.).
文摘Background:Despite significant strides in lung cancer immunotherapy,the response rates for Kirsten rat sarcoma viral oncogene homolog(KRAS)-driven lung adenocarcinoma(LUAD)patients remain limited.Fibrinogen-like protein 1(FGL1)is a newly identified immune checkpoint target,and the study of related resistance mechanisms is crucial for improving the treatment outcomes of LUAD patients.This study aimed to elucidate the potential mechanism by which FGL1 regulates the tumor microenvironment in KRAS-mutated cancer.Methods:The expression levels of FGL1 and SET1 histone methyltransferase(SET1A)in lung cancer were assessed using public databases and clinical sam-ples.Lentiviruses were constructed for transduction to overexpress or silence FGL1 in lung cancer cells and mouse models.The effects of FGL1 and Yes-associated protein(Yap)on the immunoreactivity of cytotoxic T cells in tumor tissues were evaluated using immunofluorescence staining and flow cytometry.Chromatin immunoprecipitation and dual luciferase reporter assays were used to study the SET1A-directed transcriptional program.Results:Upregulation of FGL1 expression in KRAS-mutated cancer was inversely correlated with the infiltration of CD8^(+)T cells.Mechanistically,KRAS activated extracellular signal-regulated kinase 1/2(ERK1/2),which subsequently phosphorylated SET1A and increased its stability and nuclear localization.SET1A-mediated methylation of Yap led to Yap sequestration in the nucleus,thereby promoting Yap-induced transcription of FGL1 and immune evasion in KRAS-driven LUAD.Notably,dual blockade of programmed cell death-1(PD-1)and FGL1 further increased the therapeutic efficacy of anti-PD-1 immunotherapy in LUAD patients.Conclusion:FGL1 could be used as a diagnostic biomarker of KRAS-mutated lung cancer,and targeting the Yap-FGL1 axis could increase the efficacy of anti-PD-1 immunotherapy.
基金supported by grants from the National Key Research and Development Program of China 2021YFA1100702(to B.Z.)National Natural Science Foundation of China grants 82271792(to L.S.),32200727(to L.S.)and 82071828(to C.S.)+5 种基金Innovation Capability Support Program of Shaanxi Province 2024CX-GXPT-45(to C.S.)Natural Science Foundation of Shaanxi Province 2017JM8148(to Lin Shi)Fundamental Research Funds for the Central Universities xtr072022002(to B.Z.)the National Natural Science Foundation of China 82350114(to L.Z.)the Natural Science Foundation Outstanding Youth Fund of Jiangsu Province BK20220049(to L.Z.)Suzhou Municipal Key Laboratory SZS2023005(to L.Z.).
文摘CD8^(+)T cell immune responses are regulated by multi-layer networks,while the post-translational regulation remains largely unknown.Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins.Here,by targeting the sheddase A Disintegrin and Metalloprotease(ADAM)17,we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8^(+)T cells.Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8^(+)T cells.T cellspecific deletion of ADAM17 led to a dramatic increase in effector CD8^(+)T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors.Mechanistically,ADAM17 regulated CD8^(+)T cells through cleavage of membrane CD122.ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8^(+)T cells.Intriguingly,inhibition of ADAM17 in CD8^(+)T cells improved the efficacy of chimeric antigen receptor(CAR)T cells in solid tumors.Our findings reveal a critical post-translational regulation in CD8^(+)T cells,providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.
基金supported by National Key Research and Development Program of China (2022YFF1001500)Guiding Project of Fujian Science and Technology Plan(2022N0005)
文摘Plants need to fine-tune defense responses to maintain a robust but flexible host barrier to various pathogens.Helix-loop-helix/basic helix-loop-helix(HLH/bHLH)complexes play important roles in fine-tuning plant development.However,the function of these genes in plant immunity and how they are regulated remain obscure.Here,we identified an atypical bHLH transcription factor,Oryza sativa(Os)HLH46,that interacts with rice receptor-like cytoplasmic kinase(RLCK)Os BRASSINOSTEROID-SIGNALING KINASE1-2(OsBSK1-2),which plays a key role in rice blast resistance.OsBSK1-2 stabilized OsHLH46 both in vivo and in vitro.In addition,OsHLH46 positively regulates rice blast resistance,which depends on OsBSK1-2.OsHLH46 has no transcriptional activation activity and interacts with a typical bHLH protein,OsbHLH6,which negatively regulates rice blast resistance.OsbHLH6 binds to the promoter of OsWRKY45 and inhibits its expression,while OsHLH46 suppresses the function of OsbHLH6 by blocking its DNA binding and transcriptional inhibition of OsWRKY45.Consistent with these findings,OsWRKY45 was up-regulated in OsHLH46-overexpressing plants.In addition,the oshlh46 mutant overexpressing OsbHLH6 is more susceptible to Magnaporthe oryzae than is the wild type,suggesting that OsHLH46 suppresses OsbHLH6-mediated rice blast resistance.Our results not only demonstrated that OsBSK1-2 regulates rice blast resistance via the OsHLH46/OsbHLH6 complex,but also uncovered a new mechanism for plants to fine-tune plant immunity by regulating the HLH/bHLH complex via RLCKs.
基金supported in part by the National Science and Technology Major Project(No.2021 YFC2301803)Shenzhen Fund for Guangdong Provincial High-Level Clinical Key Specialties(No.SZGSP011)+2 种基金Science and Technology Program of Shenzhen,China(No.JCYJ 20230807143411023)the clinical research project of Shenzhen Third Peoples Hospital(No.G2022044)the Teaching Quality and Teaching Reform Project of Education Department of Guangdong Province:Experimental Teaching Demonstration Center of Emerging Infectious Diseases(Y01411846).
文摘Inborn errors of the signal transducer and activator of transcription 1(STAT1)result in four types of immunodeficiency disease with varying degrees of impaired STAT1 function:autosomal recessive(AR)complete STAT1 deficiency,AR partial STAT1 deficiency,autosomal dominant(AD)STAT1 deficiency,and AD STAT1 gain-of-function(STAT1-GOF).Of which,the STAT1-GOF mutations promote a clinical syndrome of immune dysregulation characterized by recurrent infections,especially chronic mucocutaneous candidiasis(CMC)and Talaromyces marneffei infection and predisposition to humoral autoimmunity.STAT1-GOF mutations lead to enhanced phosphorylation of STAT1(pSTAT1),delayed dephosphorylation,and impaired nuclear dephosphorylation.As a result,the development of T helper(Th)17 cells is impaired,limiting the production of interleukin(IL)-17,which plays an important role in antifungal immunity.Additionally,mutations can also cause a decrease in the proportion of CD4^(+),CD8^(+),and natural killer(NK)cells.Recent research demonstrated that in the absence of overt infection,STAT-GOF mice can disrupt naïve CD4^(+)T cell homeostasis and promote expansion and differentiation of abnormal T-follicular helper/T-helper 1-like(Tfh/Th1-like)T cells and germinal center-like(GC-like)B cells,and thus reminds us of the complex molecular mechanism of autoimmune disease with/without fungal infection,which may further involve specific clinical treatment including antifungal and anti-autoimmunity therapies.In addition,sex and location of mutation were also associated with the clinical phenotype.Individuals with DNA binding domain(DBD)mutations had a higher prevalence of autoimmunity and aberrant B cell activation.Disrupted CD4^(+)T cell homeostasis occurred sooner and more robustly in females,highlighting the importance of specific treatment to normalize STAT1 expression and restore immune tolerance in patients with STAT1-GOF syndrome.Herein,we provide a comprehensive review of STAT1-GOF aiming to further clarify the regulatory mechanism of cellular and humoral immune deficiency in patients with fungal infection with or without autoimmunity.
基金supported by the National Natural Science Foundation of China(31721004,32001882)the Natural Science Foundation of Jiangsu Province(BK20190520)+1 种基金the China Post-doctoral Science Foundation(2018 M640496)the National Postdoctoral Program for Innovative Talents(BX20180142).
文摘While conventional chemical fungicides directly eliminate pathogens,plant immunity inducers activate or prime plant immunity.In recent years,considerable progress has been made in understanding the mechanisms of immune regulation in plants.The development and application of plant immunity inducers based on the principles of plant immunity represent a new field in plant protection research.In this review,we describe the mechanisms of plant immunity inducers in terms of plant immune system activation,summarize the various classes of reported plant immunity inducers(proteins,oligosaccharides,chemicals,and lipids),and review methods for the identification or synthesis of plant immunity inducers.The current situation,new strategies,and future prospects in the development and application of plant immunity inducers are also discussed.
