Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts.However,the exact molecular factors and mechanisms controlling o...Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts.However,the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely understood.Here we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion.展开更多
Mucosal surfaces that line the respiratory,gastrointestinal and genitourinary tracts are the major interfaces between the immune system and the environment.Their unique immunological landscape is characterized by the ...Mucosal surfaces that line the respiratory,gastrointestinal and genitourinary tracts are the major interfaces between the immune system and the environment.Their unique immunological landscape is characterized by the necessity of balancing tolerance to commensal microorganisms and other innocuous exposures against protection from pathogenic threats such as viruses.Numerous pathogenic viruses,including herpesviruses and retroviruses,exploit this environment to establish chronic infection.Effector and regulatory T-cell populations,including effector and resident memory T cells,play instrumental roles in mediating the transition from acute to chronic infection,where a degree of viral replication is tolerated to minimize immunopathology.Persistent antigen exposure during chronic viral infection leads to the evolution and divergence of these responses.In this review,we discuss advances in the understanding of mucosal T-cell immunity during chronic viral infections and how features of T-cell responses develop in different chronic viral infections of the mucosa.We consider how insights into T-cell immunity at mucosal surfaces could inform vaccine strategies:not only to protect hosts from chronic viral infections but also to exploit viruses that can persist within mucosal surfaces as vaccine vectors.展开更多
Interferons(IFNs)are“warning signal”cytokines released upon pathogen sensing.IFNs control the expression of interferonstimulated genes(ISGs),which are often crucial to restrict viral infections and establish a cellu...Interferons(IFNs)are“warning signal”cytokines released upon pathogen sensing.IFNs control the expression of interferonstimulated genes(ISGs),which are often crucial to restrict viral infections and establish a cellular antiviral state.1,2 Langerin(CD207),a well-known surface receptor on Langerhans cells(LC),belongs to the C-type lectin receptor(CLR)family and constitutes a major pathogen binding receptor able to regulate both innate and adaptive immune responses.3,4 Importantly,this CLR was reported as an antiviral receptor.展开更多
基金supported by the Bayerische Forschungsstiftung to B.K.the Deutsche Forschungsgemeinschaft (CRC1181 to G.K.and G.S.+3 种基金SCHE 2062/1-1 to C.S.)funded by the Wellcome Trust Investigator Award (107964/Z/15/Z)the UK Dementia Research Institutefunded by BBSRC Discovery Fellowship (BB/T009543/1)。
文摘Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts.However,the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely understood.Here we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion.
基金funded by the Wellcome Trust(Senior Research Fellowship to I.R.H.[grant 207503/Z/17/Z]the GW4-CAT-HP Fellowship to M.A-T[grant 223495/Z/21/Z])an MRC Project Grant awarded to I.R.H.[grant MR/X00922X/1].
文摘Mucosal surfaces that line the respiratory,gastrointestinal and genitourinary tracts are the major interfaces between the immune system and the environment.Their unique immunological landscape is characterized by the necessity of balancing tolerance to commensal microorganisms and other innocuous exposures against protection from pathogenic threats such as viruses.Numerous pathogenic viruses,including herpesviruses and retroviruses,exploit this environment to establish chronic infection.Effector and regulatory T-cell populations,including effector and resident memory T cells,play instrumental roles in mediating the transition from acute to chronic infection,where a degree of viral replication is tolerated to minimize immunopathology.Persistent antigen exposure during chronic viral infection leads to the evolution and divergence of these responses.In this review,we discuss advances in the understanding of mucosal T-cell immunity during chronic viral infections and how features of T-cell responses develop in different chronic viral infections of the mucosa.We consider how insights into T-cell immunity at mucosal surfaces could inform vaccine strategies:not only to protect hosts from chronic viral infections but also to exploit viruses that can persist within mucosal surfaces as vaccine vectors.
基金This work was supported in part by an ANRS grant(No.D15236)to F.P.BThis work was also supported by the Cardiff University President's Research Scholarship to M.A.C.+1 种基金grants from lSSF-WT and the Gates Foundation to V.PG.M.was the recipient of a postdoctoral fellowship from Labex EpiGenMed(Montpelier,France)and is currently supported by the ANRS.
文摘Interferons(IFNs)are“warning signal”cytokines released upon pathogen sensing.IFNs control the expression of interferonstimulated genes(ISGs),which are often crucial to restrict viral infections and establish a cellular antiviral state.1,2 Langerin(CD207),a well-known surface receptor on Langerhans cells(LC),belongs to the C-type lectin receptor(CLR)family and constitutes a major pathogen binding receptor able to regulate both innate and adaptive immune responses.3,4 Importantly,this CLR was reported as an antiviral receptor.
