Citrus canker,caused by the bacterial pathogen Xanthomonas citri ssp.citri(Xcc),has been attributed to millions of dollars in loss or damage to commercial citrus crops in subtropical production areas of the world.Sinc...Citrus canker,caused by the bacterial pathogen Xanthomonas citri ssp.citri(Xcc),has been attributed to millions of dollars in loss or damage to commercial citrus crops in subtropical production areas of the world.Since identification of resistant plants is one of the most effective methods of disease management,the ability to screen for resistant seedlings plays a key role in the production of a long-term solution to canker.Here,an inverse correlation between reactive oxygen species(ROS)production by the plant and the ability of Xcc to grow and form lesions on infected plants is reported.Based on this information,a novel screening method that can rapidly identify citrus seedlings that are less susceptible to early infection by Xcc was devised by measuring ROS accumulation triggered by a 22-amino acid sequence of the conserved N-terminal part of flagellin(flg22)from X.citri ssp.citri(Xcc-flg22).In addition to limiting disease symptoms,ROS production was also correlated with the expression of basal defense-related genes such as the pattern recognition receptors LRR8 and FLS2,the leucine-rich repeat receptor-like protein RLP12,and the defense-related gene PR1,indicating an important role for pathogen-associated molecular pattern-triggered immunity(PTI)in determining resistance to citrus canker.Moreover,the differential expression patterns observed amongst the citrus seedlings demonstrated the existence of genetic variations in the PTI response among citrus species/varieties.展开更多
In nature, plants constantly have to face pathogen attacks. However, plant disease rarely occurs due to efficient immune systems possessed by the host plants. Pathogens are perceived by two different recognition syste...In nature, plants constantly have to face pathogen attacks. However, plant disease rarely occurs due to efficient immune systems possessed by the host plants. Pathogens are perceived by two different recognition systems that initiate the so-called pattern-triggered immunity （PTI） and effector-triggered immunity （ETI）, both of which are accompanied by a set of induced defenses that usually repel pathogen attacks. Here we discuss the complex network of signaling pathways occurring during PTI, focusing on the involvement of mitogen-activated protein kinases.展开更多
Plant cells possess a two-layered immune system consisting of pattern-triggered immunity(PTI)and effector-triggered immunity(ETI), mediated by cell surface pattern-recognition receptors and intracellular nucleotide-bi...Plant cells possess a two-layered immune system consisting of pattern-triggered immunity(PTI)and effector-triggered immunity(ETI), mediated by cell surface pattern-recognition receptors and intracellular nucleotide-binding leucine-rich repeat receptors(NLRs), respectively. The CONSTITUTIVE EXPRESSION OF PR GENES 5(CPR5) nuclear pore complex protein negatively regulates ETI, including ETI-associated hypersensitive response. Here, we show that CPR5 is essential for the activation of various PTI responses in Arabidopsis, such as resistance to the non-adapted bacterium Pseudomonas syringae pv. tomato DC3000 hrc C-. In a forward-genetic screen for suppressors of cpr5, we identified the mediator protein MED4. Mutation of MED4 in cpr5 greatly restored the defective PTI of cpr5. Our findings reveal that CPR5 plays opposite roles in regulating PTI and ETI, and genetically regulates PTI via MED4.展开更多
The RING-type E3 ligase OsBBI1 regulates rice resistance against Magnaporthe oryzae through modifying cell wall defenses.In this study,we report the function of an OsBBI1 substrate,eukaryotic translation initiation fa...The RING-type E3 ligase OsBBI1 regulates rice resistance against Magnaporthe oryzae through modifying cell wall defenses.In this study,we report the function of an OsBBI1 substrate,eukaryotic translation initiation factor OseIF5A4,in rice immunity.OsBBI1 interacts with OseIF5A4 and other four members of the OseIF5A family.The RING domain in OsBBI1 and the eIF-5a domain in OseIF5A4 are critical for the OsBBI1-OseIF5A4 interaction.OsBBI1 ubiquitinates OseIF5A4 and mediates its degradation in vitro and in vivo.Moreover,the expression of OseIF5A4 was upregulated during early stage of compatible interaction but downregulated in incompatible interaction between rice and M.oryzae.Knockout of OseIF5A4 enhances rice immunity against M.oryzae and Xanthomonas oryzae pv.oryzae,boosts pattern-triggered immune responses,and strengthens pathogen-induced defense responses(e.g.,expression of defense genes,accumulation of reactive oxygen species and reinforcement of cell wall).However,overexpression of OseIF5A4 attenuates rice immunity and immune responses.These results demonstrate that OseIF5A4,a substrate of the immunity-associated E3 ligase OsBBI1,negatively regulates rice immunity against M.oryzae and X.oryzae pv.oryzae through modulating pathogen-induced defense responses,highlighting the importance of the protein translational machinery in rice immunity.展开更多
The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple c...The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple crucial for global food security,possesses six transcription factor superfamilies-AP2/ERF,bHLH,bZIP,MYB,NAC,and WRKY-that function in innate immunity against pathogens.We review their biological functions and regulatory mechanisms in rice immunity.展开更多
Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSC...Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.展开更多
Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary d...Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.展开更多
CD8^(+)T cell exhaustion,a critical challenge in the immune response to cancer,is characterized by a profound decline in the functionality of effector CD8^(+)T cells.This state of exhaustion is accompanied by the upre...CD8^(+)T cell exhaustion,a critical challenge in the immune response to cancer,is characterized by a profound decline in the functionality of effector CD8^(+)T cells.This state of exhaustion is accompanied by the upregulation of various inhibitory receptors and significant shifts in both transcriptional and epigenetic profiles,thus ultimately leading to inadequate tumor control.Therapeutic strategies aimed at reversing CD8^(+)T cell exhaustion have the potential to rejuvenate immune responses and enhance treatment efficacy.This review compiles current knowledge regarding the molecular mechanisms underlying CD8^(+)T cell exhaustion,including the roles of immune checkpoint molecules,the tumor microenvironment,metabolic reprogramming,transcription factors,and epigenetic modifications.Emerging therapeutic approaches designed to combat CD8^(+)T cell exhaustion are evaluated,with emphasis on the modulation of immune checkpoints;targeting of metabolic and transcriptional changes;and exploration of other innovative strategies,such as epigenetic editing and engineered CAR-T cells.Importantly,we expand the exhaustion concept to immune cells beyond CD8^(+)T cells,such as CD4^(+)T cells,natural killer cells,and myeloid populations,thereby highlighting the broader implications of systemic immunosuppression in the cancer context.Finally,we propose avenues for future research aimed at further elucidating the factors and molecular mechanisms associated with CD8^(+)T cell exhaustion,thereby underscoring the critical need for strategies aimed at reversing this state to improve outcomes in cancer immunotherapy.展开更多
Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept ...Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept of trained immunity has a significant impact on the field of immunology and has the potential to revolutionize how we approach vaccination and infectious disease control.Investigations into trained immunity are rapidly advanc-ing and have led to the development of new vaccines and immunotherapeutic strategies that harness the power of this phenomenon.While more investigations are needed to fully understand the mechanisms of trained immunity and its potential limitations,the prospects for its future application in clinical practice are promising.Here,we describe trained immunity as a biological process and explore the innate cues,epigenetic changes,and metabolic reprogram-ming activities that affect how trained immunity is induced.展开更多
Plants have evolved complex immune networks to adapt to survival needs,and their immune mechanisms have unique regulatory patterns to cope with different environments.In rice,the maintenance of immune balance involves...Plants have evolved complex immune networks to adapt to survival needs,and their immune mechanisms have unique regulatory patterns to cope with different environments.In rice,the maintenance of immune balance involves the synergistic action of many factors.Yue Wu et al.'s latest research results on the immunomodulatory mechanism of rice(ROD1 and the interaction between various proteins in rice)are introduced in this paper.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
Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polariz...Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal research.Methods:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in mouse.At 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol reagent.Then The harvest is subjected to transcriptome sequencing.Results:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and Il6.DEGs related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral infection.In addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of macrophages.Conclusions:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.展开更多
A recent publication by Espinosa-Carrasco et al.1has illuminated the critical roles of intratumoral immune triads-a unique cluster of CD4^(+)T cells,CD8^(+)T cells,and dendritic cells(DCs)-in mediating effective antit...A recent publication by Espinosa-Carrasco et al.1has illuminated the critical roles of intratumoral immune triads-a unique cluster of CD4^(+)T cells,CD8^(+)T cells,and dendritic cells(DCs)-in mediating effective antitumor responses.These triads ensure that CD8^(+)T cells receive the necessary help from CD4^(+)T cells,mediated via the same DC,to effectively targeting and destroying cancer cells.The article’s novel insight suggests a shift in focus from increasing the number of immune cells to optimizing their interactions within the tumor microenvironment.This groundbreaking study not only underscores the critical roles of CD4^(+)T cells and DCs,but also highlights the intricate interplay among immune cell subsets within the tumor microenvironment.展开更多
In this editorial,we comment on the article by Xu et al published in the recent issue of the World Journal of Hepatology.The hepatitis B virus(HBV)has evolved sophisticated mechanisms to evade host innate immunity,a h...In this editorial,we comment on the article by Xu et al published in the recent issue of the World Journal of Hepatology.The hepatitis B virus(HBV)has evolved sophisticated mechanisms to evade host innate immunity,a hallmark of its persistent infections.This study highlights a pivotal role for HBV-encoded microRNA,specifically HBV-miR-3,in undermining the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)-IFN signaling axis.This pathway is critical for recognizing viral DNA and subsequent production of type I interferons,key antiviral cytokines.HBV-miR-3 achieves this immune evasion by directly downregulating the expression of cGAS,an essential DNA sensor,and STING,its downstream adaptor.By silencing these components,HBV-miR-3 disrupts the activation of downstream interferon regulatory factor 3 and Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells transcription factors,thereby blunting interferon beta production and antiviral gene expression.This strategy allows HBV to persist in hepatocytes by dampening innate immune responses and contributes to immune tolerance,fostering chronic infection.Understanding the role of HBV-miR-3 provides novel insights into HBV pathogenesis and identifies potential therapeutic targets to restore antiviral immunity.Targeting HBV-miR-3 or reactivating the cGAS-STING-IFN pathway could offer promising strategies to counteract HBV immune evasion and resolve chronic infection.展开更多
Infectious bursal disease(IBD)is an acute,highly contagious disease that affects chicks(Müller et al.2003).IBD mainly damages the immune organs of chicks,especially the central immune organ,causing immune suppres...Infectious bursal disease(IBD)is an acute,highly contagious disease that affects chicks(Müller et al.2003).IBD mainly damages the immune organs of chicks,especially the central immune organ,causing immune suppression in diseased chicks(Muller et al.2012).The pathogenic infectious bursal disease virus(IBDV)is a member of the Avira virus genus in the Birnaviridae family.(Harkness et al.1975;Dobos et al.1979;Müller et al.1979).IBDV is prevalent worldwide,causing serious economic losses to the global poultry industry.Currently,vaccination remains the most cost-effective way to prevent IBDV.展开更多
Interleukin-1(IL-1)was the first interleukin identified as a potent proinflammatory and multifunctional molecule involved in innate immune responses against microbes,as well as in conditions of tissue injury associate...Interleukin-1(IL-1)was the first interleukin identified as a potent proinflammatory and multifunctional molecule involved in innate immune responses against microbes,as well as in conditions of tissue injury associated with infections and sterile conditions.IL-1 is part of a large system,the IL-1 system,comprising a family of ligands that act as agonists,receptor antagonists,and antiinflammatory cytokines,as well as a family of receptors that includes signaling receptor complexes,decoy receptors and negative regulators.All the members of the IL-1 system are involved in inflammatory diseases,innate and adaptive immune responses,conditions associated with dysmetabolism,and cancer by affecting both the tumor microenvironment and cancer cells.The deregulated or excessive activation of several pathways associated with the IL-1 system may lead to detrimental inflammatory or immune reactions,including autoinflammatory,autoimmune,infectious and degenerative diseases.The negative regulation of the IL-1 system mediated by antagonists,decoy receptors,scavengers,and dominant-negative molecules plays nonredundant roles in controlling these conditions.Owing to the central role of IL-1 in the pathogenesis of inflammation-driven diseases,IL-1 blocking agents are approved for clinical use in several inflammatory conditions,and inhibitory agents for other members of the family are under development.Here,the complexity of the IL-1 system,the involvement of its different members in inflammation-driven diseases,and the therapeutic approaches to target members of pathways associated with these conditions are presented and discussed.展开更多
Objective:Lung cancer is the leading cause of cancer-related deaths worldwide.Chemotherapy is associated with side effects,such as damage to myeloid cells and a reduction in the number of immune cells in patients.In a...Objective:Lung cancer is the leading cause of cancer-related deaths worldwide.Chemotherapy is associated with side effects,such as damage to myeloid cells and a reduction in the number of immune cells in patients.In addition,tumor cells hijack the mitochondria of immune cells through tunnel nanotubes,thereby weakening immune ability.Methods:In this study the effects of direct mitochondria transplantation on cancer cell proliferation and chemotherapeutic sensitivity were determined,as well as anti-tumor immunity in in vitro and in vivo lung cancer models.Results:A combination of mitochondrial transplantation and cisplatin chemotherapy was shown for the first time to significantly improve immune infiltration of advanced non-small cell lung cancer(NSCLC)and overcome the shortcomings of cisplatin chemotherapy,including damage to myeloid cells and a reduction in the number of immune cells.Conclusions:The findings of the current study provide valuable recommendations for enhancing immune infiltration and augmenting anti-tumor efficacy during chemotherapy in advanced NSCLC.In addition,the findings support“mitochondrial transfer”as a novel paradigm in tumor treatment.展开更多
In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing i...In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing is complex and involves a coordinated series of biological events,including inflammation,cell proliferation,and tissue remodeling.The innate immune system is important in the early stages of wound repair,with inflammation being a crucial initial phase in tissue rege-neration.However,the inflammatory response should be regulated,as excessive or dysregulated inflammation can impair healing.Platelet concentrates,specifi-cally PRF,have originated as promising tools to optimize the tissue repair process.PRF is a second-generation platelet concentrate,and the release of growth factors(GFs)plays a determining role in several aspects of wound healing,including promoting cell proliferation,stimulating angiogenesis,and modulating inflam-mation.PRF forms a fibrin matrix that entraps platelets and GFs.This structure allows for their sustained release over time,which is believed to provide a more favorable microenvironment for tissue repair.Recent research by Sá-Oliveira et al has provided valuable evidence supporting the efficacy of PRF in promoting wound healing.Their study,conducted on an animal model,demonstrated that PRF-based dressings were more effective in accelerating wound closure in the early stages of the healing process,enhancing tissue repair,and modulating the inflammatory response.We explore how PRF's unique properties contribute to a more controlled and effective healing process.By examining these findings,we aim to highlight PRF's potential as a promising therapeutic strategy for improved wound management.展开更多
Remodeling plant intracellular nucleotide-binding leucine-rich repeat immune receptors(NLRs)to engineer synthetic disease-resistance genes has emerged as a promising approach to achieving broad-spectrum disease resist...Remodeling plant intracellular nucleotide-binding leucine-rich repeat immune receptors(NLRs)to engineer synthetic disease-resistance genes has emerged as a promising approach to achieving broad-spectrum disease resistance.But strategies for expanding NLR recognition spectra[[1],[2],[3],[4],[5]]are often limited by the rapid evolution of pathogens and pests.In our recent study,we developed an innovative strategy to engineer broad-spectrum,durable and complete disease resistance in plants by remodeling autoactive NLRs into protease-activated switches[6].展开更多
Objective:To explore the imaging characteristics changes of pulmonary infections in patients with hypo-immunity and analyze the correlation between NLR,PCT levels and their severity.Methods:This study included 80 pati...Objective:To explore the imaging characteristics changes of pulmonary infections in patients with hypo-immunity and analyze the correlation between NLR,PCT levels and their severity.Methods:This study included 80 patients with hypo-immunity and pulmonary infections who were diagnosed and treated at our hospital from October 2022 to October 2024.Imaging examinations were performed on the patients.Subsequently,the patients were divided into a severe group and a mild group based on the severity of their disease.Univariate analysis was conducted,and variables with statistical significance from the univariate analysis were included in a multivariate logistic regression analysis to clarify the correlation between plasma NLR,PCT levels,and their severity.Results:Imaging examinations revealed that ground-glass opacities in the lungs were centered around the hilum,with patchy or map-like distributions accompanied by reticular shadows.The affected areas and normal lung areas were interspersed,with a tendency to merge.Some patients also developed pneumothorax.Ground-glass opacities were the most characteristic manifestation,which could also present as reticular shadows,interstitial thickening,miliary shadows,multiple small nodules,intrathoracic lymphadenopathy,and a small amount of pleural effusion.In the correlation analysis,NLR and PCT were statistically significant in the univariate analysis(p<0.05).When included in the multivariate logistic regression analysis,NLR(OR=2.846,95%CI:2.402-3.358)and PCT(OR=1.958,95%CI:1.554-2.601)were found to be positively correlated with the severity of pulmonary infections in patients with hypo-immunity.Conclusion:The imaging manifestations of patients with impaired immune function are complex and diverse,primarily including patchy,linear,massive,cavitary,and diffuse lesions,among other forms.These manifestations not only assist physicians in identifying the presence of pulmonary infections but also provide crucial information for diagnosing the type,severity,and complications of the infections.The levels of NLR(Neutrophil-to-Lymphocyte Ratio)and PCT(Procalcitonin)exhibit a positive correlation with the severity of pulmonary infections in patients with impaired immune function,warranting significant attention.展开更多
基金Funding was provided by the U.S.Department of Agriculture。
文摘Citrus canker,caused by the bacterial pathogen Xanthomonas citri ssp.citri(Xcc),has been attributed to millions of dollars in loss or damage to commercial citrus crops in subtropical production areas of the world.Since identification of resistant plants is one of the most effective methods of disease management,the ability to screen for resistant seedlings plays a key role in the production of a long-term solution to canker.Here,an inverse correlation between reactive oxygen species(ROS)production by the plant and the ability of Xcc to grow and form lesions on infected plants is reported.Based on this information,a novel screening method that can rapidly identify citrus seedlings that are less susceptible to early infection by Xcc was devised by measuring ROS accumulation triggered by a 22-amino acid sequence of the conserved N-terminal part of flagellin(flg22)from X.citri ssp.citri(Xcc-flg22).In addition to limiting disease symptoms,ROS production was also correlated with the expression of basal defense-related genes such as the pattern recognition receptors LRR8 and FLS2,the leucine-rich repeat receptor-like protein RLP12,and the defense-related gene PR1,indicating an important role for pathogen-associated molecular pattern-triggered immunity(PTI)in determining resistance to citrus canker.Moreover,the differential expression patterns observed amongst the citrus seedlings demonstrated the existence of genetic variations in the PTI response among citrus species/varieties.
文摘In nature, plants constantly have to face pathogen attacks. However, plant disease rarely occurs due to efficient immune systems possessed by the host plants. Pathogens are perceived by two different recognition systems that initiate the so-called pattern-triggered immunity （PTI） and effector-triggered immunity （ETI）, both of which are accompanied by a set of induced defenses that usually repel pathogen attacks. Here we discuss the complex network of signaling pathways occurring during PTI, focusing on the involvement of mitogen-activated protein kinases.
基金supported by grants from the National Key R&D Program of China (2021YFA1300701)National Natural Science Foundation of China (32120103004, 32270282)the Hainan Excellent Talent Team, and the State Key Laboratory of Plant Genomics (SKLPG2016B-2)。
文摘Plant cells possess a two-layered immune system consisting of pattern-triggered immunity(PTI)and effector-triggered immunity(ETI), mediated by cell surface pattern-recognition receptors and intracellular nucleotide-binding leucine-rich repeat receptors(NLRs), respectively. The CONSTITUTIVE EXPRESSION OF PR GENES 5(CPR5) nuclear pore complex protein negatively regulates ETI, including ETI-associated hypersensitive response. Here, we show that CPR5 is essential for the activation of various PTI responses in Arabidopsis, such as resistance to the non-adapted bacterium Pseudomonas syringae pv. tomato DC3000 hrc C-. In a forward-genetic screen for suppressors of cpr5, we identified the mediator protein MED4. Mutation of MED4 in cpr5 greatly restored the defective PTI of cpr5. Our findings reveal that CPR5 plays opposite roles in regulating PTI and ETI, and genetically regulates PTI via MED4.
基金supported by grants from the National Natural Science Foundation of China(32072403 and 31871945)the National Key Research and Development Program of China(2016YFD0100600).
文摘The RING-type E3 ligase OsBBI1 regulates rice resistance against Magnaporthe oryzae through modifying cell wall defenses.In this study,we report the function of an OsBBI1 substrate,eukaryotic translation initiation factor OseIF5A4,in rice immunity.OsBBI1 interacts with OseIF5A4 and other four members of the OseIF5A family.The RING domain in OsBBI1 and the eIF-5a domain in OseIF5A4 are critical for the OsBBI1-OseIF5A4 interaction.OsBBI1 ubiquitinates OseIF5A4 and mediates its degradation in vitro and in vivo.Moreover,the expression of OseIF5A4 was upregulated during early stage of compatible interaction but downregulated in incompatible interaction between rice and M.oryzae.Knockout of OseIF5A4 enhances rice immunity against M.oryzae and Xanthomonas oryzae pv.oryzae,boosts pattern-triggered immune responses,and strengthens pathogen-induced defense responses(e.g.,expression of defense genes,accumulation of reactive oxygen species and reinforcement of cell wall).However,overexpression of OseIF5A4 attenuates rice immunity and immune responses.These results demonstrate that OseIF5A4,a substrate of the immunity-associated E3 ligase OsBBI1,negatively regulates rice immunity against M.oryzae and X.oryzae pv.oryzae through modulating pathogen-induced defense responses,highlighting the importance of the protein translational machinery in rice immunity.
基金supported by Research Program for Agricultural Science and Technology Development,Republic of Korea(PJ01570601)the Fellowship Program(PJ01661001)of the National Institute of Agricultural Sciences,Republic of KoreaRural Development Administration,Republic of Korea.
文摘The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple crucial for global food security,possesses six transcription factor superfamilies-AP2/ERF,bHLH,bZIP,MYB,NAC,and WRKY-that function in innate immunity against pathogens.We review their biological functions and regulatory mechanisms in rice immunity.
基金supported by Natural Science Foundation of Guangdong Province,China(2022A1515011575)National Natural Science Foundation of China,China(81873154)President Foundation of Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,China(1202103010)。
文摘Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.
文摘Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82171810)the Program of Shandong Provincial Scientific and Technological Development of Traditional Chinese Medicine(Grant No.M-2023210)。
文摘CD8^(+)T cell exhaustion,a critical challenge in the immune response to cancer,is characterized by a profound decline in the functionality of effector CD8^(+)T cells.This state of exhaustion is accompanied by the upregulation of various inhibitory receptors and significant shifts in both transcriptional and epigenetic profiles,thus ultimately leading to inadequate tumor control.Therapeutic strategies aimed at reversing CD8^(+)T cell exhaustion have the potential to rejuvenate immune responses and enhance treatment efficacy.This review compiles current knowledge regarding the molecular mechanisms underlying CD8^(+)T cell exhaustion,including the roles of immune checkpoint molecules,the tumor microenvironment,metabolic reprogramming,transcription factors,and epigenetic modifications.Emerging therapeutic approaches designed to combat CD8^(+)T cell exhaustion are evaluated,with emphasis on the modulation of immune checkpoints;targeting of metabolic and transcriptional changes;and exploration of other innovative strategies,such as epigenetic editing and engineered CAR-T cells.Importantly,we expand the exhaustion concept to immune cells beyond CD8^(+)T cells,such as CD4^(+)T cells,natural killer cells,and myeloid populations,thereby highlighting the broader implications of systemic immunosuppression in the cancer context.Finally,we propose avenues for future research aimed at further elucidating the factors and molecular mechanisms associated with CD8^(+)T cell exhaustion,thereby underscoring the critical need for strategies aimed at reversing this state to improve outcomes in cancer immunotherapy.
文摘Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept of trained immunity has a significant impact on the field of immunology and has the potential to revolutionize how we approach vaccination and infectious disease control.Investigations into trained immunity are rapidly advanc-ing and have led to the development of new vaccines and immunotherapeutic strategies that harness the power of this phenomenon.While more investigations are needed to fully understand the mechanisms of trained immunity and its potential limitations,the prospects for its future application in clinical practice are promising.Here,we describe trained immunity as a biological process and explore the innate cues,epigenetic changes,and metabolic reprogram-ming activities that affect how trained immunity is induced.
基金support of the National Natural Science Foundation of China(32472594)the Independent Deployment Project of Institute of Zoology,Chinese Academy of Sciences(2023IOZ010).
文摘Plants have evolved complex immune networks to adapt to survival needs,and their immune mechanisms have unique regulatory patterns to cope with different environments.In rice,the maintenance of immune balance involves the synergistic action of many factors.Yue Wu et al.'s latest research results on the immunomodulatory mechanism of rice(ROD1 and the interaction between various proteins in rice)are introduced in this paper.
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CAMs innovation Fund for Medical Sciences,Grant/Award Number:2022-12M-CoV19-005National Key Projects,Grant/Award Number:2023YFF0724900 and 2021YFF0702802。
文摘Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal research.Methods:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in mouse.At 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol reagent.Then The harvest is subjected to transcriptome sequencing.Results:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and Il6.DEGs related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral infection.In addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of macrophages.Conclusions:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.
文摘A recent publication by Espinosa-Carrasco et al.1has illuminated the critical roles of intratumoral immune triads-a unique cluster of CD4^(+)T cells,CD8^(+)T cells,and dendritic cells(DCs)-in mediating effective antitumor responses.These triads ensure that CD8^(+)T cells receive the necessary help from CD4^(+)T cells,mediated via the same DC,to effectively targeting and destroying cancer cells.The article’s novel insight suggests a shift in focus from increasing the number of immune cells to optimizing their interactions within the tumor microenvironment.This groundbreaking study not only underscores the critical roles of CD4^(+)T cells and DCs,but also highlights the intricate interplay among immune cell subsets within the tumor microenvironment.
文摘In this editorial,we comment on the article by Xu et al published in the recent issue of the World Journal of Hepatology.The hepatitis B virus(HBV)has evolved sophisticated mechanisms to evade host innate immunity,a hallmark of its persistent infections.This study highlights a pivotal role for HBV-encoded microRNA,specifically HBV-miR-3,in undermining the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)-IFN signaling axis.This pathway is critical for recognizing viral DNA and subsequent production of type I interferons,key antiviral cytokines.HBV-miR-3 achieves this immune evasion by directly downregulating the expression of cGAS,an essential DNA sensor,and STING,its downstream adaptor.By silencing these components,HBV-miR-3 disrupts the activation of downstream interferon regulatory factor 3 and Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells transcription factors,thereby blunting interferon beta production and antiviral gene expression.This strategy allows HBV to persist in hepatocytes by dampening innate immune responses and contributes to immune tolerance,fostering chronic infection.Understanding the role of HBV-miR-3 provides novel insights into HBV pathogenesis and identifies potential therapeutic targets to restore antiviral immunity.Targeting HBV-miR-3 or reactivating the cGAS-STING-IFN pathway could offer promising strategies to counteract HBV immune evasion and resolve chronic infection.
基金supported by grants from the National Key R&D Program of China(2022YFD1801000)the Natural Science Foundation of Shanghai,China(24ZR1479200)。
文摘Infectious bursal disease(IBD)is an acute,highly contagious disease that affects chicks(Müller et al.2003).IBD mainly damages the immune organs of chicks,especially the central immune organ,causing immune suppression in diseased chicks(Muller et al.2012).The pathogenic infectious bursal disease virus(IBDV)is a member of the Avira virus genus in the Birnaviridae family.(Harkness et al.1975;Dobos et al.1979;Müller et al.1979).IBDV is prevalent worldwide,causing serious economic losses to the global poultry industry.Currently,vaccination remains the most cost-effective way to prevent IBDV.
基金support from Associazione Italiana per la Ricerca sul Cancro(AIRC):AIRC IG 30875 to CGAIRC IG 30335 to SJ.The Italian Ministry of Health RF2021-12372202 to SJ,European Unionfunding within the Ministry of Health(PNRR-Italian network of excellence for advanced diagnosis,Project no.PNC-E3-2022-23683266 PNC-HLS-DA+1 种基金Project PNRR-MAD-2022-12375947,Project PNRR-MAD-202312377789)IDC is financed by the HIgh Profile POst doc program-HIPPO Fondi 5×1000 Italian Ministry of University and Research.
文摘Interleukin-1(IL-1)was the first interleukin identified as a potent proinflammatory and multifunctional molecule involved in innate immune responses against microbes,as well as in conditions of tissue injury associated with infections and sterile conditions.IL-1 is part of a large system,the IL-1 system,comprising a family of ligands that act as agonists,receptor antagonists,and antiinflammatory cytokines,as well as a family of receptors that includes signaling receptor complexes,decoy receptors and negative regulators.All the members of the IL-1 system are involved in inflammatory diseases,innate and adaptive immune responses,conditions associated with dysmetabolism,and cancer by affecting both the tumor microenvironment and cancer cells.The deregulated or excessive activation of several pathways associated with the IL-1 system may lead to detrimental inflammatory or immune reactions,including autoinflammatory,autoimmune,infectious and degenerative diseases.The negative regulation of the IL-1 system mediated by antagonists,decoy receptors,scavengers,and dominant-negative molecules plays nonredundant roles in controlling these conditions.Owing to the central role of IL-1 in the pathogenesis of inflammation-driven diseases,IL-1 blocking agents are approved for clinical use in several inflammatory conditions,and inhibitory agents for other members of the family are under development.Here,the complexity of the IL-1 system,the involvement of its different members in inflammation-driven diseases,and the therapeutic approaches to target members of pathways associated with these conditions are presented and discussed.
基金supported by the National Natural Science Foundation of China(Grant No.81922030)the International Cooperation Project of the Belt and Road(Grant No.20400750600)+1 种基金the Construction Project of Shanghai TCMintegrated Innovative Flagship Hospital[Grant No.ZY(2021-2023)-0205-05,ZXXT-202203]the Shanghai Municipal Commission of Health and Family Plan(Grant No.201840056).
文摘Objective:Lung cancer is the leading cause of cancer-related deaths worldwide.Chemotherapy is associated with side effects,such as damage to myeloid cells and a reduction in the number of immune cells in patients.In addition,tumor cells hijack the mitochondria of immune cells through tunnel nanotubes,thereby weakening immune ability.Methods:In this study the effects of direct mitochondria transplantation on cancer cell proliferation and chemotherapeutic sensitivity were determined,as well as anti-tumor immunity in in vitro and in vivo lung cancer models.Results:A combination of mitochondrial transplantation and cisplatin chemotherapy was shown for the first time to significantly improve immune infiltration of advanced non-small cell lung cancer(NSCLC)and overcome the shortcomings of cisplatin chemotherapy,including damage to myeloid cells and a reduction in the number of immune cells.Conclusions:The findings of the current study provide valuable recommendations for enhancing immune infiltration and augmenting anti-tumor efficacy during chemotherapy in advanced NSCLC.In addition,the findings support“mitochondrial transfer”as a novel paradigm in tumor treatment.
基金Supported by The Oman Ministry of Higher Education,Research,and Innovation,No.BFP/RGP/HSS/24/015.
文摘In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing is complex and involves a coordinated series of biological events,including inflammation,cell proliferation,and tissue remodeling.The innate immune system is important in the early stages of wound repair,with inflammation being a crucial initial phase in tissue rege-neration.However,the inflammatory response should be regulated,as excessive or dysregulated inflammation can impair healing.Platelet concentrates,specifi-cally PRF,have originated as promising tools to optimize the tissue repair process.PRF is a second-generation platelet concentrate,and the release of growth factors(GFs)plays a determining role in several aspects of wound healing,including promoting cell proliferation,stimulating angiogenesis,and modulating inflam-mation.PRF forms a fibrin matrix that entraps platelets and GFs.This structure allows for their sustained release over time,which is believed to provide a more favorable microenvironment for tissue repair.Recent research by Sá-Oliveira et al has provided valuable evidence supporting the efficacy of PRF in promoting wound healing.Their study,conducted on an animal model,demonstrated that PRF-based dressings were more effective in accelerating wound closure in the early stages of the healing process,enhancing tissue repair,and modulating the inflammatory response.We explore how PRF's unique properties contribute to a more controlled and effective healing process.By examining these findings,we aim to highlight PRF's potential as a promising therapeutic strategy for improved wound management.
基金supported by the Biological Breeding-National Science and Technology Major Project(2024ZD04077).
文摘Remodeling plant intracellular nucleotide-binding leucine-rich repeat immune receptors(NLRs)to engineer synthetic disease-resistance genes has emerged as a promising approach to achieving broad-spectrum disease resistance.But strategies for expanding NLR recognition spectra[[1],[2],[3],[4],[5]]are often limited by the rapid evolution of pathogens and pests.In our recent study,we developed an innovative strategy to engineer broad-spectrum,durable and complete disease resistance in plants by remodeling autoactive NLRs into protease-activated switches[6].
基金Pathogen Distribution,Imaging Features,and Clinical Manifestations of Pulmonary Infections in Patients with Impaired Immune Function(Project No.:2023-1-NS-017)。
文摘Objective:To explore the imaging characteristics changes of pulmonary infections in patients with hypo-immunity and analyze the correlation between NLR,PCT levels and their severity.Methods:This study included 80 patients with hypo-immunity and pulmonary infections who were diagnosed and treated at our hospital from October 2022 to October 2024.Imaging examinations were performed on the patients.Subsequently,the patients were divided into a severe group and a mild group based on the severity of their disease.Univariate analysis was conducted,and variables with statistical significance from the univariate analysis were included in a multivariate logistic regression analysis to clarify the correlation between plasma NLR,PCT levels,and their severity.Results:Imaging examinations revealed that ground-glass opacities in the lungs were centered around the hilum,with patchy or map-like distributions accompanied by reticular shadows.The affected areas and normal lung areas were interspersed,with a tendency to merge.Some patients also developed pneumothorax.Ground-glass opacities were the most characteristic manifestation,which could also present as reticular shadows,interstitial thickening,miliary shadows,multiple small nodules,intrathoracic lymphadenopathy,and a small amount of pleural effusion.In the correlation analysis,NLR and PCT were statistically significant in the univariate analysis(p<0.05).When included in the multivariate logistic regression analysis,NLR(OR=2.846,95%CI:2.402-3.358)and PCT(OR=1.958,95%CI:1.554-2.601)were found to be positively correlated with the severity of pulmonary infections in patients with hypo-immunity.Conclusion:The imaging manifestations of patients with impaired immune function are complex and diverse,primarily including patchy,linear,massive,cavitary,and diffuse lesions,among other forms.These manifestations not only assist physicians in identifying the presence of pulmonary infections but also provide crucial information for diagnosing the type,severity,and complications of the infections.The levels of NLR(Neutrophil-to-Lymphocyte Ratio)and PCT(Procalcitonin)exhibit a positive correlation with the severity of pulmonary infections in patients with impaired immune function,warranting significant attention.
