Type I and III interferons(IFNs)are essential for antiviral immunity and act through two different but complimentary pathways.First,IFNs activate intracellular antimicrobial programs by triggering the upregulation of ...Type I and III interferons(IFNs)are essential for antiviral immunity and act through two different but complimentary pathways.First,IFNs activate intracellular antimicrobial programs by triggering the upregulation of a broad repertoire of viral restriction factors.Second,IFNs activate innate and adaptive immunity.Dysregulation of IFN production can lead to severe immune system dysfunction.It is thus crucial to identify and characterize the cellular sources of IFNs,their effects,and their regulation to promote their beneficial effects and limit their detrimental effects,which can depend on the nature of the infected or diseased tissues,as we will discuss.Plasmacytoid dendritic cells(pDCs)can produce large amounts of all IFN subtypes during viral infection.pDCs are resistant to infection by many different viruses,thus inhibiting the immune evasion mechanisms of viruses that target IFN production or their downstream responses.Therefore,pDCs are considered essential for the control of viral infections and the establishment of protective immunity.A thorough bibliographical survey showed that,in most viral infections,despite being major IFN producers,pDCs are actually dispensable for host resistance,which is achieved by multiple IFN sources depending on the tissue.Moreover,primary innate and adaptive antiviral immune responses are only transiently affected in the absence of pDCs.More surprisingly,pDCs and their IFNs can be detrimental in some viral infections or autoimmune diseases.This makes the conservation of pDCs during vertebrate evolution an enigma and thus raises outstanding questions about their role not only in viral infections but also in other diseases and under physiological conditions.展开更多
T cell activation is a main component of adaptive immunity,which involves two types of signals transmitted by key immune receptors upon engagement with their respective ligands present on the antigen-presenting cells(...T cell activation is a main component of adaptive immunity,which involves two types of signals transmitted by key immune receptors upon engagement with their respective ligands present on the antigen-presenting cells(APCs)[1].The first signal is induced via the T cell receptor(TCR)upon binding to antigenic peptide–major histocompatibility complex(pMHC);the second signal is induced via the costimulatory receptors,the prototype of which is CD28,which can bind to either B7-1(also known as CD80)or B7-2(also known as CD86)[2,3].展开更多
基金supported by a fellowship from the French Ministry of Research and Higher Education.C.G.is supported by the French National Research Agency(no.ANR-21-CO15-0044-01,“DECITIP”,to E.T.).All the authors acknowledge institutional support from CNRS,INSERM,and Aix-Marseille Université.
文摘Type I and III interferons(IFNs)are essential for antiviral immunity and act through two different but complimentary pathways.First,IFNs activate intracellular antimicrobial programs by triggering the upregulation of a broad repertoire of viral restriction factors.Second,IFNs activate innate and adaptive immunity.Dysregulation of IFN production can lead to severe immune system dysfunction.It is thus crucial to identify and characterize the cellular sources of IFNs,their effects,and their regulation to promote their beneficial effects and limit their detrimental effects,which can depend on the nature of the infected or diseased tissues,as we will discuss.Plasmacytoid dendritic cells(pDCs)can produce large amounts of all IFN subtypes during viral infection.pDCs are resistant to infection by many different viruses,thus inhibiting the immune evasion mechanisms of viruses that target IFN production or their downstream responses.Therefore,pDCs are considered essential for the control of viral infections and the establishment of protective immunity.A thorough bibliographical survey showed that,in most viral infections,despite being major IFN producers,pDCs are actually dispensable for host resistance,which is achieved by multiple IFN sources depending on the tissue.Moreover,primary innate and adaptive antiviral immune responses are only transiently affected in the absence of pDCs.More surprisingly,pDCs and their IFNs can be detrimental in some viral infections or autoimmune diseases.This makes the conservation of pDCs during vertebrate evolution an enigma and thus raises outstanding questions about their role not only in viral infections but also in other diseases and under physiological conditions.
基金supported by institutional grants from INSERM and CNRS and by specific grants from CNRS(CNRS IRP CHOLESTIM)the Agence Nationale de la Recherche(ANR-10-BLAN-1509+1 种基金ANR-11-LABX-Investissement d’Avenir Labex-INFORMANR-17CE15-0032)。
文摘T cell activation is a main component of adaptive immunity,which involves two types of signals transmitted by key immune receptors upon engagement with their respective ligands present on the antigen-presenting cells(APCs)[1].The first signal is induced via the T cell receptor(TCR)upon binding to antigenic peptide–major histocompatibility complex(pMHC);the second signal is induced via the costimulatory receptors,the prototype of which is CD28,which can bind to either B7-1(also known as CD80)or B7-2(also known as CD86)[2,3].
