title: Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection.
abstract: Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.
authors.affiliation: Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Hôpital St.-Luc, Montréal, Québec, Canada.
authors.forename: Elias A
authors.initials: EA
authors.lastname: Said
authors.forename: Franck P
authors.initials: FP
authors.lastname: Dupuy
authors.forename: Lydie
authors.initials: L
authors.lastname: Trautmann
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Far
authors.forename: Brenna J
authors.initials: BJ
authors.lastname: Hill
authors.forename: Alessandra
authors.initials: A
authors.lastname: Noto
authors.forename: Petronela
authors.initials: P
authors.lastname: Ancuta
authors.forename: Yoav
authors.initials: Y
authors.lastname: Peretz
authors.forename: Simone G
authors.initials: SG
authors.lastname: Fonseca
authors.forename: Julien
authors.initials: J
authors.lastname: Van Grevenynghe
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Boulassel
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.forename: Naglaa H
authors.initials: NH
authors.lastname: Shoukry
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Elias K
authors.initials: EK
authors.lastname: Haddad
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D060890:B7-H1 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology / Q000821:virology*; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D009000:Monocytes / Q000276:immunology / Q000502:physiology*; D010766:Phosphorylation; D017452:Receptors, IgG / Q000276:immunology / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D014766:Viremia / Q000276:immunology / Q000503:physiopathology
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D017452:Receptors, IgG; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10