Dendritic cells （DCs） are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate immune response. DCs have a unique character of ...Dendritic cells （DCs） are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate immune response. DCs have a unique character of immunoregulation. DC-SIGN, a molecule designated as CD209, is one member of the C-type lectin superfamily. It is not only a pattern recognition receptor but implicated in immunoregulation of DCs. DC-SIGN has become hotspot of recent studies because of its important role in mediating DC adhesion, migration, inflammation, activating primary T cell, triggering immune response and participating in immune escape of pathogens and tumors. These studies on DC-SIGN involved in primary and secondary immune response and relevant mechanism will certainly provide us with a new method in treating and preventing certain diseases.展开更多
Dendritic-cell-specific intercellular adhesion molecule-3-grabbing non-integrin(DC-SIGN;CD209)has an important role in mediating adherence of Mycobacteria species,including M.tuberculosis and M.bovis BCG to human dend...Dendritic-cell-specific intercellular adhesion molecule-3-grabbing non-integrin(DC-SIGN;CD209)has an important role in mediating adherence of Mycobacteria species,including M.tuberculosis and M.bovis BCG to human dendritic cells and macrophages,in which these bacteria can survive intracellularly.DC-SIGN is a C-type lectin,and interactions with mycobacterial cells are believed to occur via mannosylated structures on the mycobacterial surface.Recent studies suggest more varied modes of binding to multiple mycobacterial ligands.Here we identify,by affinity chromatography and mass-spectrometry,four novel ligands of M.bovis BCG that bind to DC-SIGN.The novel ligands are chaperone protein DnaK,60 kDa chaperonin-1(Cpn60.1),glyceraldehyde-3 phosphate dehydrogenase(GAPDH)and lipoprotein lprG.Other published work strongly suggests that these are on the cell surface.Of these ligands,lprG appears to bind DC-SIGN via typical proteinglycan interactions,but DnaK and Cpn60.1 binding do not show evidence of carbohydrate-dependent interactions.LprG was also identified as a ligand for DC-SIGNR(L-SIGN;CD299)and the M.tuberculosis orthologue of lprG has been found previously to interact with human toll-like receptor 2.Collectively,these findings offer new targets for combating mycobacterial adhesion and within-host survival,and reinforce the role of DCSIGN as an important host ligand in mycobacterial infection.展开更多
Objective To review the recent developments in and research into binding receptors of hepatitis C virus (HCV) and especially the role of dendritic cell-specitic adhesion receptor (DC-SIGN) in HCV.Data sources Both C...Objective To review the recent developments in and research into binding receptors of hepatitis C virus (HCV) and especially the role of dendritic cell-specitic adhesion receptor (DC-SIGN) in HCV.Data sources Both Chinese- and English-languge literature was searched using MEDLINE (2000-2003) and the databank of Chinese-language literature (2000-2003).Study selection Relevant articles on DC-SIGN and HCV binding receptors in recent domestic and foreign literature were selected.Data extraction Data were mainly extracted from 40 articles which are listed in the references section of this review. Results DC-SIGN, a dendritic cell-specific adhesion receptor and a type Ⅱ transmembrane mannose-binding C-type lectin, is very important in the function of dendritic cells (DC), both in mediating nave T cell interactions through ICAM-3 and as a rolling receptor that mediates the DC-specific ICAM-2-dependent migration processes. It can be used by HCV and other viral and bacterial pathogens including human immunodeficiency virus (HIV), Ebola virus, CMV and Mycobacterium tuberculosis to facilitate infection. Both DC-SIGN and DC-SIGNR can act either in cis, by concentrating virus on target cells, or in trans, by transmission of bound virus to a target cell expressing appropriate entry receptors. Recent report showed that DC-SIGN not only plays a role in entry into DC, HCV E2 interaction with DC-SIGN might also be detrimental to the interaction of DC with T cells during antigen presentation. Conclusions DC-SIGNs are high-affinity binding receptors for HCV.The clinical strategies that target DC-SIGN may be successful in restricting HCV dissemination and pathogenesis as well as directing the migration of DCs to manipulate appropriate immune responses in autoimmunity and tumorigenic situations.展开更多
C-type lectins(CTLs)represent a large family of soluble and membrane-bound proteins which bind calcium dependently via carbohydrate recognition domains(CRDs)to glycan residues presented on the surface of a variety of ...C-type lectins(CTLs)represent a large family of soluble and membrane-bound proteins which bind calcium dependently via carbohydrate recognition domains(CRDs)to glycan residues presented on the surface of a variety of pathogens.The deconvolution of a cell’s glycan code by CTLs underpins several important physiological processes in mammals such as pathogen neutralization and opsonization,leukocyte trafficking,and the inflammatory response.However,as our knowledge of CTLs has developed it has become apparent that the role of this innate immune family of proteins can be double-edged,where some pathogens have developed approaches to subvert and exploit CTL interactions to promote infection and sustain the pathological state.Equally,CTL interactions with host glycoproteins can contribute to inflammatory diseases such as arthritis and cancer whereby,in certain contexts,they exacerbate inflammation and drive malignant progression.This review discusses the‘dual agent’roles of some of the major mammalian CTLs in both resolving and promoting infection,inflammation and inflammatory disease and highlights opportunities and emerging approaches for their therapeutic modulation.展开更多
基金supported by National Natural Science Foundation of China(No.39970340,No.30570865)Natural Science Foundation of Shanghai(No.02ZB14041,No.034119916).
文摘Dendritic cells （DCs） are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate immune response. DCs have a unique character of immunoregulation. DC-SIGN, a molecule designated as CD209, is one member of the C-type lectin superfamily. It is not only a pattern recognition receptor but implicated in immunoregulation of DCs. DC-SIGN has become hotspot of recent studies because of its important role in mediating DC adhesion, migration, inflammation, activating primary T cell, triggering immune response and participating in immune escape of pathogens and tumors. These studies on DC-SIGN involved in primary and secondary immune response and relevant mechanism will certainly provide us with a new method in treating and preventing certain diseases.
文摘Dendritic-cell-specific intercellular adhesion molecule-3-grabbing non-integrin(DC-SIGN;CD209)has an important role in mediating adherence of Mycobacteria species,including M.tuberculosis and M.bovis BCG to human dendritic cells and macrophages,in which these bacteria can survive intracellularly.DC-SIGN is a C-type lectin,and interactions with mycobacterial cells are believed to occur via mannosylated structures on the mycobacterial surface.Recent studies suggest more varied modes of binding to multiple mycobacterial ligands.Here we identify,by affinity chromatography and mass-spectrometry,four novel ligands of M.bovis BCG that bind to DC-SIGN.The novel ligands are chaperone protein DnaK,60 kDa chaperonin-1(Cpn60.1),glyceraldehyde-3 phosphate dehydrogenase(GAPDH)and lipoprotein lprG.Other published work strongly suggests that these are on the cell surface.Of these ligands,lprG appears to bind DC-SIGN via typical proteinglycan interactions,but DnaK and Cpn60.1 binding do not show evidence of carbohydrate-dependent interactions.LprG was also identified as a ligand for DC-SIGNR(L-SIGN;CD299)and the M.tuberculosis orthologue of lprG has been found previously to interact with human toll-like receptor 2.Collectively,these findings offer new targets for combating mycobacterial adhesion and within-host survival,and reinforce the role of DCSIGN as an important host ligand in mycobacterial infection.
基金ThisprojectwassupportedbyagrantfromtheNationalNaturalScienceFoundationofChina (No 3 0 170 82 2 )
文摘Objective To review the recent developments in and research into binding receptors of hepatitis C virus (HCV) and especially the role of dendritic cell-specitic adhesion receptor (DC-SIGN) in HCV.Data sources Both Chinese- and English-languge literature was searched using MEDLINE (2000-2003) and the databank of Chinese-language literature (2000-2003).Study selection Relevant articles on DC-SIGN and HCV binding receptors in recent domestic and foreign literature were selected.Data extraction Data were mainly extracted from 40 articles which are listed in the references section of this review. Results DC-SIGN, a dendritic cell-specific adhesion receptor and a type Ⅱ transmembrane mannose-binding C-type lectin, is very important in the function of dendritic cells (DC), both in mediating nave T cell interactions through ICAM-3 and as a rolling receptor that mediates the DC-specific ICAM-2-dependent migration processes. It can be used by HCV and other viral and bacterial pathogens including human immunodeficiency virus (HIV), Ebola virus, CMV and Mycobacterium tuberculosis to facilitate infection. Both DC-SIGN and DC-SIGNR can act either in cis, by concentrating virus on target cells, or in trans, by transmission of bound virus to a target cell expressing appropriate entry receptors. Recent report showed that DC-SIGN not only plays a role in entry into DC, HCV E2 interaction with DC-SIGN might also be detrimental to the interaction of DC with T cells during antigen presentation. Conclusions DC-SIGNs are high-affinity binding receptors for HCV.The clinical strategies that target DC-SIGN may be successful in restricting HCV dissemination and pathogenesis as well as directing the migration of DCs to manipulate appropriate immune responses in autoimmunity and tumorigenic situations.
基金D.A.M.is supported by the Howard Ostin Fund and the University Hospitals Coventry and Warwickshire Renal Medicine Department.J.N.A.is funded by a grant from Cancer Research UK(DCRPGF\100009)and is the recipient of a Cancer Research Institute/Wade F.B.Thompson CLIP grant(CRI3645).
文摘C-type lectins(CTLs)represent a large family of soluble and membrane-bound proteins which bind calcium dependently via carbohydrate recognition domains(CRDs)to glycan residues presented on the surface of a variety of pathogens.The deconvolution of a cell’s glycan code by CTLs underpins several important physiological processes in mammals such as pathogen neutralization and opsonization,leukocyte trafficking,and the inflammatory response.However,as our knowledge of CTLs has developed it has become apparent that the role of this innate immune family of proteins can be double-edged,where some pathogens have developed approaches to subvert and exploit CTL interactions to promote infection and sustain the pathological state.Equally,CTL interactions with host glycoproteins can contribute to inflammatory diseases such as arthritis and cancer whereby,in certain contexts,they exacerbate inflammation and drive malignant progression.This review discusses the‘dual agent’roles of some of the major mammalian CTLs in both resolving and promoting infection,inflammation and inflammatory disease and highlights opportunities and emerging approaches for their therapeutic modulation.
