title: Japanese encephalitis virus expands regulatory T cells by increasing the expression of PD-L1 on dendritic cells.
abstract: The mechanisms underlying Japanese encephalitis virus (JEV) pathogenesis need to be thoroughly explored to delineate therapeutic approaches. It is believed that JEV manipulates the innate and adaptive compartments of the host's immune system to evade immune response and cross the blood-brain barrier. The present study was thus designed to investigate the functional modulation of DCs after exposure to JEV and to assess the consequences on CD4(+) T-lymphocyte functions. Human monocyte-derived DCs were either infected with 1 MOI of live virus, UV-inactivated virus, or were mock-infected. Replication-competent JEV induced a significant increase in the expression of maturation markers 48 h postinfection, along with that of programmed cell death 1 ligand 1 (PD-L1; also called B7-H1 and CD274). JEV-infected DCs expanded the Treg cells in allogenic mixed lymphocyte reactions. The expansion of Treg cells by JEV-infected DCs was significantly reduced upon blocking PD-L1 using an antagonist. In addition, JEV-infected DCs significantly altered the proliferation and reduced the polarization of Th cells toward the Th1-cell phenotype. The results, for the first time, suggest that JEV evades the host's immune system by modulating the crosstalk between DCs and T lymphocytes via the PD-L1 axis.
authors.affiliation: Centre de Recherche des Cordeliers, INSERM, UMR S 1138, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 1138, Paris, France; Centre de Recherche des Cordeliers, Université Paris Descartes, UMR S 1138, Paris, France.
authors.forename: Nimesh
authors.initials: N
authors.lastname: Gupta
authors.forename: Pushpa
authors.initials: P
authors.lastname: Hegde
authors.forename: Maxime
authors.initials: M
authors.lastname: Lecerf
authors.forename: Minu
authors.initials: M
authors.lastname: Nain
authors.forename: Manpreet
authors.initials: M
authors.lastname: Kaur
authors.forename: Manjula
authors.initials: M
authors.lastname: Kalia
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Vrati
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D060890:B7-H1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004672:Encephalitis, Japanese / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion / Q000235:genetics / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000943:Antigens, Differentiation; D060890:B7-H1 Antigen; C423236:CD274 protein, human
keywords: Host-pathogen interactions; Immune evasion; Infectious diseases; PD-L1; Regulatory T cells