Tuberculosis,caused by Mycobacterium tuberculosis(Mtb),is a critical global health issue that is complicated by the ability of the pathogen to delay the host’s T-cell immune response.This delay in T-cell recruitment ...Tuberculosis,caused by Mycobacterium tuberculosis(Mtb),is a critical global health issue that is complicated by the ability of the pathogen to delay the host’s T-cell immune response.This delay in T-cell recruitment to the site of infection is a pivotal survival strategy for Mtb,allowing it to establish a persistent chronic infection.To investigate the underlying mechanisms,this study focused on Mtb’s exploitation of host tryptophan metabolism.Mtb upregulates indoleamine 2,3-dioxygenase 1(IDO1)in inflammatory macrophages,thereby increasing kynurenine(Kyn)production.Kyn then activates the aryl hydrocarbon receptor(AhR),leading to the upregulation of suppressor of cytokine signaling 3 and subsequent inhibition of the JAK-STAT1 signaling pathway.This results in reduced secretion of the chemokines CXCL9 and CXCL10,which are crucial for T-cell recruitment to the lungs.Supported by in vivo mouse models,our findings reveal that disrupting this pathway through AhR knockout significantly enhances T-cell infiltration and activity,thereby undermining Mtb-induced immunosuppression.In contrast,additional Kyn injection obviously inhibited T-cell infiltration and activity.These results highlight potential therapeutic targets of AhR and IDO1,offering new avenues for enhancing the host immune response against tuberculosis and guiding future vaccine development efforts.展开更多
Chemical defoliation stands as the ultimate tool in enabling the mechanical harvest of cotton, offering economic and environmental advantages. However, the underlying molecular mechanism that triggers leaf abscission ...Chemical defoliation stands as the ultimate tool in enabling the mechanical harvest of cotton, offering economic and environmental advantages. However, the underlying molecular mechanism that triggers leaf abscission through defoliant remains unsolved. In this study, we meticulously constructed a transcriptomic atlas through single-nucleus mRNA sequencing (snRNA-seq) of the abscission zone (AZ) from cotton petiole. We identified two newly-formed cell types, abscission cells and protection layer cells in cotton petiole AZ after defoliant treatment. GhRLF1 (RAPID LEAF FALLING 1), as one of the members of the cytokinin oxidase/dehydrogenase (CKX) gene family, was further characterized as a key marker gene unique to the abscission cells following defoliant treatment. Overexpression of GhRLF1 resulted in reduced cytokinin accumulation and accelerated leaf abscission. Conversely, CRISPR/Cas9-mediated loss of GhRLF1 function appeared to delay this process. Its interacting regulators, GhWRKY70, acting as “Pioneer” activator, and GhMYB108, acting as “Successor” activator, orchestrate a sequential modulation of GhWRKY70/GhMYB108–GhRLF1–CTK (cytokinin) within the AZ to regulate cotton leaf abscission. GhRLF1 not only regulates leaf abscission but also reduces cotton yield. Consequently, transgenic lines that exhibit rapid leaf falling and require less defoliant but show unaffected cotton yield were developed for mechanical harvesting. This was achieved using a defoliant-induced petiole-specific promoter, proPER21, to drive GhRLF1 (proPER21::RLF1). This pioneering biotechnology offers a new strategy for the chemical defoliation of machine-harvested cotton, ensuring stable production and reducing leaf debris in harvested cotton, thereby enhancing environmental sustainability.展开更多
基金supported by the National Key Research and Development Program of China(2022YFC2302901)the National Natural Science Foundation of China(82272346,82072243,82202530)+1 种基金the Sponsored by Beijing Nova Program(20220484169,20230484295)the Provincial Key Research and Development Program of Jiangsu in Social Development(BE2023718).
文摘Tuberculosis,caused by Mycobacterium tuberculosis(Mtb),is a critical global health issue that is complicated by the ability of the pathogen to delay the host’s T-cell immune response.This delay in T-cell recruitment to the site of infection is a pivotal survival strategy for Mtb,allowing it to establish a persistent chronic infection.To investigate the underlying mechanisms,this study focused on Mtb’s exploitation of host tryptophan metabolism.Mtb upregulates indoleamine 2,3-dioxygenase 1(IDO1)in inflammatory macrophages,thereby increasing kynurenine(Kyn)production.Kyn then activates the aryl hydrocarbon receptor(AhR),leading to the upregulation of suppressor of cytokine signaling 3 and subsequent inhibition of the JAK-STAT1 signaling pathway.This results in reduced secretion of the chemokines CXCL9 and CXCL10,which are crucial for T-cell recruitment to the lungs.Supported by in vivo mouse models,our findings reveal that disrupting this pathway through AhR knockout significantly enhances T-cell infiltration and activity,thereby undermining Mtb-induced immunosuppression.In contrast,additional Kyn injection obviously inhibited T-cell infiltration and activity.These results highlight potential therapeutic targets of AhR and IDO1,offering new avenues for enhancing the host immune response against tuberculosis and guiding future vaccine development efforts.
基金supported by funding from the National Key Project of Research and the Development Plan of China(2021YFF1000103)the National Natural Science Foundation of China(32171942)The development fund for Xinjiang talents XL,and the Agricultural GG Project of Xinjiang Production and Construction Corps(NYHXGG,2023AA102).
文摘Chemical defoliation stands as the ultimate tool in enabling the mechanical harvest of cotton, offering economic and environmental advantages. However, the underlying molecular mechanism that triggers leaf abscission through defoliant remains unsolved. In this study, we meticulously constructed a transcriptomic atlas through single-nucleus mRNA sequencing (snRNA-seq) of the abscission zone (AZ) from cotton petiole. We identified two newly-formed cell types, abscission cells and protection layer cells in cotton petiole AZ after defoliant treatment. GhRLF1 (RAPID LEAF FALLING 1), as one of the members of the cytokinin oxidase/dehydrogenase (CKX) gene family, was further characterized as a key marker gene unique to the abscission cells following defoliant treatment. Overexpression of GhRLF1 resulted in reduced cytokinin accumulation and accelerated leaf abscission. Conversely, CRISPR/Cas9-mediated loss of GhRLF1 function appeared to delay this process. Its interacting regulators, GhWRKY70, acting as “Pioneer” activator, and GhMYB108, acting as “Successor” activator, orchestrate a sequential modulation of GhWRKY70/GhMYB108–GhRLF1–CTK (cytokinin) within the AZ to regulate cotton leaf abscission. GhRLF1 not only regulates leaf abscission but also reduces cotton yield. Consequently, transgenic lines that exhibit rapid leaf falling and require less defoliant but show unaffected cotton yield were developed for mechanical harvesting. This was achieved using a defoliant-induced petiole-specific promoter, proPER21, to drive GhRLF1 (proPER21::RLF1). This pioneering biotechnology offers a new strategy for the chemical defoliation of machine-harvested cotton, ensuring stable production and reducing leaf debris in harvested cotton, thereby enhancing environmental sustainability.
