Antigen-presentation via major histocompatibility complex(MHC)to T cells is the key event to initiate adaptive immune responses.In teleosts,as in mammals,the main types of professional antigen-presenting cells(APCs)ar...Antigen-presentation via major histocompatibility complex(MHC)to T cells is the key event to initiate adaptive immune responses.In teleosts,as in mammals,the main types of professional antigen-presenting cells(APCs)are dendritic cells(DCs),monocytes/macrophages,and B cells.In the current study,flow cytometry,immunostaining and qPCR have been used to show that neutrophils in the teleost fish Atlantic salmon(Salmo salar L.)have antigen-presenting properties.The neutrophils were positive for MHC class II,CD83 and CD80/86,and upon in vitro bacterial exposure,gene expression analysis of purified neutrophils showed that IL-12p40,which is essential for proliferation of naïve T cells,was highly upregulated at both 6 and 24 h post bacterial exposure.Based on presence of MHC class II and upregulation of molecules involved in antigen presentation and T cell activation,we suggest that neutrophils in Atlantic salmon have potential to function as professional APCs.This work makes an important basis for further exploring the potential of using neutrophils to develop new,targeted immunoprophylactic measures.展开更多
Traditionally,macroautophagy(autophagy)is viewed as a pathway of cell survival.Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods o...Traditionally,macroautophagy(autophagy)is viewed as a pathway of cell survival.Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of stress.Interestingly,autophagy can also directly intersect with,and impact,other major pathways of cellular function.Here,we will review the contribution of autophagy to pathways of antigen presentation.The autophagy machinery acts to modulate both MHCⅠ and MHCⅡ antigen presentation.As such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.展开更多
The liver is an important immunological organ that controls systemic tolerance.The liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and maintenance.Orches...The liver is an important immunological organ that controls systemic tolerance.The liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and maintenance.Orchestrating the immune response in homeostasis depends on a healthy and well-toned immunological liver microenvironment,which Is maintained by the crosstalk of liver-resident antigen-presenting cells and intrahepatic and liver-infiltrating leukocytes.In response to pathogens or autoantigens,tolerance is disrupted by unknown mechanisms.Intrahepatic parenchymal and nonparenchymal cells exhibit unique antigen-presenting properties.The presentation of microbial and endogenous lipid-,metabolite-and peptide-derived antigens from the gut via conventional and nonconventional mechanisms can educate intrahepatic immune cells and elicit effector responses or tolerance.Perturbation of this balance results in autoimmune liver diseases,such as autoimmune hepatitis,primary biliary cholangitis,and primary sclerosing cholangitis.Although the exact etiologies of these autoimmune liver diseases are unknown,it is thought that the disruption of tolerance towards self-antigens and microbial metabolites and lipids,as well as alterations in bile acid composition,may result in changes in effector cell activation and polarization and may reduce or impair protective antiinflammatory regulatory T and B cell responses.Additionally,the canonical and noncanonical transmission of antigens and antigen:MHC complexes via trogocytosis or extracellular vesicles between different(non)immune cells in the liver may play a role in the induction of hepatic inflammation and tolerance.Here,we summarize emerging aspects of antigen presentation,autoantibody production,and the application of novel therapeutic approaches in the characterization and treatment of autoimmune liver diseases.展开更多
Vaccination is the most effective way to prevent coronavirus disease 2019(COVID-19).Vaccine development approaches consist of viral vector vaccines,DNA vaccine,RNA vaccine,live attenuated virus,and recombinant protein...Vaccination is the most effective way to prevent coronavirus disease 2019(COVID-19).Vaccine development approaches consist of viral vector vaccines,DNA vaccine,RNA vaccine,live attenuated virus,and recombinant proteins,which elicit a specific immune response.The use of nanoparticles displaying antigen is one of the alternative approaches to conventional vaccines.This is due to the fact that nano-based vaccines are stable,able to target,form images,and offer an opportunity to enhance the immune responses.The diameters of ultrafine nanoparticles are in the range of 1–100 nm.The application of nanotechnology on vaccine design provides precise fabrication of nanomaterials with desirable properties and ability to eliminate undesirable features.To be successful,nanomaterials must be uptaken into the cell,especially into the target and able to modulate cellular functions at the subcellular levels.The advantages of nano-based vaccines are the ability to protect a cargo such as RNA,DNA,protein,or synthesis substance and have enhanced stability in a broad range of pH,ambient temperatures,and humidity for long-term storage.Moreover,nano-based vaccines can be engineered to overcome biological barriers such as nonspecific distribution in order to elicit functions in antigen presenting cells.In this review,we will summarize on the developing COVID-19 vaccine strategies and how the nanotechnology can enhance antigen presentation and strong immunogenicity using advanced technology in nanocarrier to deliver antigens.The discussion about their safe,effective,and affordable vaccines to immunize against COVID-19 will be highlighted.展开更多
文摘Antigen-presentation via major histocompatibility complex(MHC)to T cells is the key event to initiate adaptive immune responses.In teleosts,as in mammals,the main types of professional antigen-presenting cells(APCs)are dendritic cells(DCs),monocytes/macrophages,and B cells.In the current study,flow cytometry,immunostaining and qPCR have been used to show that neutrophils in the teleost fish Atlantic salmon(Salmo salar L.)have antigen-presenting properties.The neutrophils were positive for MHC class II,CD83 and CD80/86,and upon in vitro bacterial exposure,gene expression analysis of purified neutrophils showed that IL-12p40,which is essential for proliferation of naïve T cells,was highly upregulated at both 6 and 24 h post bacterial exposure.Based on presence of MHC class II and upregulation of molecules involved in antigen presentation and T cell activation,we suggest that neutrophils in Atlantic salmon have potential to function as professional APCs.This work makes an important basis for further exploring the potential of using neutrophils to develop new,targeted immunoprophylactic measures.
基金supported by a National Health and Medical Research Council of Australia Career Development Award.
文摘Traditionally,macroautophagy(autophagy)is viewed as a pathway of cell survival.Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of stress.Interestingly,autophagy can also directly intersect with,and impact,other major pathways of cellular function.Here,we will review the contribution of autophagy to pathways of antigen presentation.The autophagy machinery acts to modulate both MHCⅠ and MHCⅡ antigen presentation.As such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.
基金supported by funding from the German Research Foundation(DFG),Collaborative Research grants within the CRC841(SFB841:"Liver inflammation:Infection,immune regulation und consequences"),projects B01 to A.K.H.and G.T.,B09 to L.D.the Clinical Research Group KF0306("Primary Sclerosing Cholangitis"),project 04 to G.T.
文摘The liver is an important immunological organ that controls systemic tolerance.The liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and maintenance.Orchestrating the immune response in homeostasis depends on a healthy and well-toned immunological liver microenvironment,which Is maintained by the crosstalk of liver-resident antigen-presenting cells and intrahepatic and liver-infiltrating leukocytes.In response to pathogens or autoantigens,tolerance is disrupted by unknown mechanisms.Intrahepatic parenchymal and nonparenchymal cells exhibit unique antigen-presenting properties.The presentation of microbial and endogenous lipid-,metabolite-and peptide-derived antigens from the gut via conventional and nonconventional mechanisms can educate intrahepatic immune cells and elicit effector responses or tolerance.Perturbation of this balance results in autoimmune liver diseases,such as autoimmune hepatitis,primary biliary cholangitis,and primary sclerosing cholangitis.Although the exact etiologies of these autoimmune liver diseases are unknown,it is thought that the disruption of tolerance towards self-antigens and microbial metabolites and lipids,as well as alterations in bile acid composition,may result in changes in effector cell activation and polarization and may reduce or impair protective antiinflammatory regulatory T and B cell responses.Additionally,the canonical and noncanonical transmission of antigens and antigen:MHC complexes via trogocytosis or extracellular vesicles between different(non)immune cells in the liver may play a role in the induction of hepatic inflammation and tolerance.Here,we summarize emerging aspects of antigen presentation,autoantibody production,and the application of novel therapeutic approaches in the characterization and treatment of autoimmune liver diseases.
基金OCSC Royal Thai Government-UCAS Scholarship under research collaboration between National Nanotechnology Center(NANOTEC),Thailand,and National Center for Nanoscience and Technology,China(No.P1852764)This work was also supported by the National Natural Science Foundation of China(NSFC)key projects(Nos.31630027 and 32030060)+4 种基金NSFC international collaboration key project(No.51861135103)NSFC-German Research Foundation(DFG)project(No.31761133013)The authors also appreciate the support by“the Beijing-Tianjin-Hebei Basic Research Cooperation Project”(No.19JCZDJC64100)National Key Research&Development Program of China(No.2018YFE0117800)The authors are grateful for Prof.Dr.S.Seraphin at the Professional Authorship Center,Thailand National Science,and Technology Development Agency(NSTDA)for fruitful discussions on the manuscript preparation.
文摘Vaccination is the most effective way to prevent coronavirus disease 2019(COVID-19).Vaccine development approaches consist of viral vector vaccines,DNA vaccine,RNA vaccine,live attenuated virus,and recombinant proteins,which elicit a specific immune response.The use of nanoparticles displaying antigen is one of the alternative approaches to conventional vaccines.This is due to the fact that nano-based vaccines are stable,able to target,form images,and offer an opportunity to enhance the immune responses.The diameters of ultrafine nanoparticles are in the range of 1–100 nm.The application of nanotechnology on vaccine design provides precise fabrication of nanomaterials with desirable properties and ability to eliminate undesirable features.To be successful,nanomaterials must be uptaken into the cell,especially into the target and able to modulate cellular functions at the subcellular levels.The advantages of nano-based vaccines are the ability to protect a cargo such as RNA,DNA,protein,or synthesis substance and have enhanced stability in a broad range of pH,ambient temperatures,and humidity for long-term storage.Moreover,nano-based vaccines can be engineered to overcome biological barriers such as nonspecific distribution in order to elicit functions in antigen presenting cells.In this review,we will summarize on the developing COVID-19 vaccine strategies and how the nanotechnology can enhance antigen presentation and strong immunogenicity using advanced technology in nanocarrier to deliver antigens.The discussion about their safe,effective,and affordable vaccines to immunize against COVID-19 will be highlighted.