Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection.
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.
Said
Elias A
EA
Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Hôpital St.-Luc, Montréal, Québec, Canada.
Dupuy
Franck P
FP
Trautmann
Lydie
L
Zhang
Yuwei
Y
Shi
Yu
Y
El-Far
Mohamed
M
Hill
Brenna J
BJ
Noto
Alessandra
A
Ancuta
Petronela
P
Peretz
Yoav
Y
Fonseca
Simone G
SG
Van Grevenynghe
Julien
J
Boulassel
Mohamed R
MR
Bruneau
Julie
J
Shoukry
Naglaa H
NH
Routy
Jean-Pierre
JP
Douek
Daniel C
DC
Haddad
Elias K
EK
Sekaly
Rafick-Pierre
RP
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
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