Excitatory amino acid transporters(EAATs) are responsible for excitatory amino acid transportation and are associated with auto-immune diseases in the central nervous system and peripheral tissues.However, the subcell...Excitatory amino acid transporters(EAATs) are responsible for excitatory amino acid transportation and are associated with auto-immune diseases in the central nervous system and peripheral tissues.However, the subcellular location and function of EAAT2 in macrophages are still obscure. In this study,we demonstrated that LPS stimulation increases expression of EAAT2(coded by Slc1a2) via NF-κB signaling. EAAT2 is necessary for inflammatory macrophage polarization through sustaining mTORC1 activation. Mechanistically, lysosomal EAAT2 mediates lysosomal glutamate and aspartate efflux to maintain V-ATPase activation, which sustains macropinocytosis and mTORC1. We also found that mice with myeloid depletion of Slc1a2 show alleviated inflammatory responses in LPS-induced systemic inflammation and high-fat diet induced obesity. Notably, patients with type Ⅱ diabetes(T2D) have a higher level of expression of lysosomal EAAT2 and activation of mTORC1 in blood macrophages. Taken together, our study links the subcellular location of amino acid transporters with the fate decision of immune cells,which provides potential therapeutic targets for the treatment of inflammatory diseases.展开更多
Dietary nutrients and the gut microbiota are increasingly recognized to cross-regulate and entrain each other,and thus affect host health and immune-mediated diseases.Here,we systematically review the current understa...Dietary nutrients and the gut microbiota are increasingly recognized to cross-regulate and entrain each other,and thus affect host health and immune-mediated diseases.Here,we systematically review the current understanding linking dietary nutrients to gut microbiota-host immune interactions,emphasizing how this axis might influence host immunity in health and diseases.Of relevance,we highlight that the implications of gut microbiota-targeted dietary intervention could be harnessed in orchestrating a spectrum of immune-associated diseases.展开更多
Due to the immature gastrointestinal immune system,weaning piglets are highly susceptible to pathogens,e.g.,enterotoxigenic Escherichia coli(ETEC).Generally,pathogens activate the immune cells(e.g.,macrophages)and sha...Due to the immature gastrointestinal immune system,weaning piglets are highly susceptible to pathogens,e.g.,enterotoxigenic Escherichia coli(ETEC).Generally,pathogens activate the immune cells(e.g.,macrophages)and shape intracellular metabolism(including amino acid metabolism);nevertheless,the metabolic cues of tryptophan(especially melatonin pathway)in directing porcine macrophage function during ETEC infection remain unclear.Therefore,this study aimed to investigate the changes in the serotonin pathway of porcine macrophages during ETEC infection and the effect of melatonin on porcine macrophage functions.Porcine macrophages(3D4/21 cells)were infected with ETEC,and the change of serotonin pathway was analysed by reverse transcription PCR and metabolomic analysis.The effect of melatonin on porcine macrophage function was also studied with proteomic analysis.In order to investigate the effect of melatonin on bacterial clearance function of porcine macrophages during ETEC infection,methods such as bacterial counting,reverse transcription PCR and western blotting were used to detect the corresponding indicators.The results showed that ETEC infection blocked melatonin production in porcine macrophages(P<0.05)which is largely associated with the heat-stable enterotoxin b(STb)of ETEC(P<0.05).Interestingly,melatonin altered porcine macrophage functions,including bacteriostatic and bactericidal activities based on proteomic analysis.In addition,melatonin pretreatment significantly reduced extracellular lactate dehydrogenase(LDH)activity(P<0.05),indicating that melatonin also attenuated ETEC-triggered macrophage death.Moreover,melatonin pretreatment resulted in the decrease of viable ETEC in 3D4/21 cells(P<0.05),suggesting that melatonin enhances bacterial clearance of porcine macrophages.These results suggest that melatonin is particularly important in shaping porcine macrophage function during ETEC infection.展开更多
Intestinal microbes are closely associated with host health,depending on metabolic crosstalk between the microbiota and host.Tryptophan metabolism is one of the best examples of metabolic crosstalk between intestinal ...Intestinal microbes are closely associated with host health,depending on metabolic crosstalk between the microbiota and host.Tryptophan metabolism is one of the best examples of metabolic crosstalk between intestinal microbiota and host;however,our understanding about the influence of intestinal microbiota on host tryptophan metabolism is limited.Thus,we established germ-free(GF)pig models to systemically explore the influence of intestinal microbiota on tryptophan metabolism.Five GF pigs were kept in GF conditions throughout the experiment(GF group).Six GF pigs were transplanted with fecal microbiota from donor sows to act as control pigs.Compared with control pigs,the GF pigs had remarkable alterations in tryptophan metabolism.The differential metabolites(P<0.05)were mainly found in the liver,circulation system and large intestine.Notably,the alteration of metabolites in tryptophan metabolism varied among organs,especially for the serotonin pathway.In GF pigs,tryptophan and kynurenine in the large intestine and 5-hydroxytryptophan in most organs were increased(P<0.05),while metabolites in the indole pathway in most organs were decreased(P<0.05).Collectively,our study reveals changes in tryptophan metabolism in GF pigs,highlighting the critical role of gut microbes in shaping host tryptophan metabolism.展开更多
Recent discoveries have underscored the cross-talk between intestinal microbes and their hosts.Notably,intestinal microbiota impacts the development,physiological function and social behavior of hosts.This influence u...Recent discoveries have underscored the cross-talk between intestinal microbes and their hosts.Notably,intestinal microbiota impacts the development,physiological function and social behavior of hosts.This influence usually revolves around the microbiota-gut-brain axis(MGBA).In tbis review,we firstly outline the impacts of the host on colonization of intestinal microorganisms,and then highlight the influence of intestinal microbiota on hosts focusing on short-chain fatty acid(SCFA)and tryptophan metabolite-mediated MGBA.We also discuss the intervention of intestinal microbial metabolism by dietary sup-plements,which may provide new strategies for improving the welfare and production of pigs.Overall,we summarize a state-of-the-art theory that gut microbiome affects brain functions via metabolites from dietary macronutrients.展开更多
基金supported by the National Natural Science Foundation of China (32225047 and U22A20510)Laboratory of Lingnan Modern Agriculture Project (NT2021005)+1 种基金National Center of Technology Innovation for Pigs (NCTIP-XD/B13)double first-class discipline promotion project (2023B10564001)。
文摘Excitatory amino acid transporters(EAATs) are responsible for excitatory amino acid transportation and are associated with auto-immune diseases in the central nervous system and peripheral tissues.However, the subcellular location and function of EAAT2 in macrophages are still obscure. In this study,we demonstrated that LPS stimulation increases expression of EAAT2(coded by Slc1a2) via NF-κB signaling. EAAT2 is necessary for inflammatory macrophage polarization through sustaining mTORC1 activation. Mechanistically, lysosomal EAAT2 mediates lysosomal glutamate and aspartate efflux to maintain V-ATPase activation, which sustains macropinocytosis and mTORC1. We also found that mice with myeloid depletion of Slc1a2 show alleviated inflammatory responses in LPS-induced systemic inflammation and high-fat diet induced obesity. Notably, patients with type Ⅱ diabetes(T2D) have a higher level of expression of lysosomal EAAT2 and activation of mTORC1 in blood macrophages. Taken together, our study links the subcellular location of amino acid transporters with the fate decision of immune cells,which provides potential therapeutic targets for the treatment of inflammatory diseases.
基金supported by the National Key Research and Development Program of China(2021YFD1300700,2021YFD1300201,2022YFA1304201)the National Natural Science Foundation of China(32225047,U22A20510,32125036,32172750,31972596,31902170,31630074,32272916,32102567)+4 种基金the Laboratory of Lingnan Modern Agriculture Project(NT2021005)the China Agricultural Research System of MOF and MARA(CARS-35)the Key Research and Development Project of Hainan Province(ZDYF2021XDNY177)the 111 Project(B16044)the Program for Shaanxi Science and Technology(2022KJXX-13).
文摘Dietary nutrients and the gut microbiota are increasingly recognized to cross-regulate and entrain each other,and thus affect host health and immune-mediated diseases.Here,we systematically review the current understanding linking dietary nutrients to gut microbiota-host immune interactions,emphasizing how this axis might influence host immunity in health and diseases.Of relevance,we highlight that the implications of gut microbiota-targeted dietary intervention could be harnessed in orchestrating a spectrum of immune-associated diseases.
文摘Due to the immature gastrointestinal immune system,weaning piglets are highly susceptible to pathogens,e.g.,enterotoxigenic Escherichia coli(ETEC).Generally,pathogens activate the immune cells(e.g.,macrophages)and shape intracellular metabolism(including amino acid metabolism);nevertheless,the metabolic cues of tryptophan(especially melatonin pathway)in directing porcine macrophage function during ETEC infection remain unclear.Therefore,this study aimed to investigate the changes in the serotonin pathway of porcine macrophages during ETEC infection and the effect of melatonin on porcine macrophage functions.Porcine macrophages(3D4/21 cells)were infected with ETEC,and the change of serotonin pathway was analysed by reverse transcription PCR and metabolomic analysis.The effect of melatonin on porcine macrophage function was also studied with proteomic analysis.In order to investigate the effect of melatonin on bacterial clearance function of porcine macrophages during ETEC infection,methods such as bacterial counting,reverse transcription PCR and western blotting were used to detect the corresponding indicators.The results showed that ETEC infection blocked melatonin production in porcine macrophages(P<0.05)which is largely associated with the heat-stable enterotoxin b(STb)of ETEC(P<0.05).Interestingly,melatonin altered porcine macrophage functions,including bacteriostatic and bactericidal activities based on proteomic analysis.In addition,melatonin pretreatment significantly reduced extracellular lactate dehydrogenase(LDH)activity(P<0.05),indicating that melatonin also attenuated ETEC-triggered macrophage death.Moreover,melatonin pretreatment resulted in the decrease of viable ETEC in 3D4/21 cells(P<0.05),suggesting that melatonin enhances bacterial clearance of porcine macrophages.These results suggest that melatonin is particularly important in shaping porcine macrophage function during ETEC infection.
基金National Key R&D Program of China(2021YFD1300700)Laboratory of Lingnan Modern Agriculture Project(NT2021005)。
文摘Intestinal microbes are closely associated with host health,depending on metabolic crosstalk between the microbiota and host.Tryptophan metabolism is one of the best examples of metabolic crosstalk between intestinal microbiota and host;however,our understanding about the influence of intestinal microbiota on host tryptophan metabolism is limited.Thus,we established germ-free(GF)pig models to systemically explore the influence of intestinal microbiota on tryptophan metabolism.Five GF pigs were kept in GF conditions throughout the experiment(GF group).Six GF pigs were transplanted with fecal microbiota from donor sows to act as control pigs.Compared with control pigs,the GF pigs had remarkable alterations in tryptophan metabolism.The differential metabolites(P<0.05)were mainly found in the liver,circulation system and large intestine.Notably,the alteration of metabolites in tryptophan metabolism varied among organs,especially for the serotonin pathway.In GF pigs,tryptophan and kynurenine in the large intestine and 5-hydroxytryptophan in most organs were increased(P<0.05),while metabolites in the indole pathway in most organs were decreased(P<0.05).Collectively,our study reveals changes in tryptophan metabolism in GF pigs,highlighting the critical role of gut microbes in shaping host tryptophan metabolism.
基金the National Natural Science Foundation of China(31922079,31872365,and 31790411)Guangdong Basic and Applied Basic Research Foundation(2019B1515210002).
文摘Recent discoveries have underscored the cross-talk between intestinal microbes and their hosts.Notably,intestinal microbiota impacts the development,physiological function and social behavior of hosts.This influence usually revolves around the microbiota-gut-brain axis(MGBA).In tbis review,we firstly outline the impacts of the host on colonization of intestinal microorganisms,and then highlight the influence of intestinal microbiota on hosts focusing on short-chain fatty acid(SCFA)and tryptophan metabolite-mediated MGBA.We also discuss the intervention of intestinal microbial metabolism by dietary sup-plements,which may provide new strategies for improving the welfare and production of pigs.Overall,we summarize a state-of-the-art theory that gut microbiome affects brain functions via metabolites from dietary macronutrients.
