Upregulation of indoleamine 2,3-dioxygenase in hepatitis C virus infection.
Indoleamine 2,3-dioxygenase (IDO) is induced by proinflammatory cytokines and by CTLA-4-expressing T cells and constitutes an important mediator of peripheral immune tolerance. In chronic hepatitis C, we found upregulation of IDO expression in the liver and an increased serum kynurenine/tryptophan ratio (a reflection of IDO activity). Huh7 cells supporting hepatitis C virus (HCV) replication expressed higher levels of IDO mRNA than noninfected cells when stimulated with gamma interferon or when cocultured with activated T cells. In infected chimpanzees, hepatic IDO expression decreased in animals that cured the infection, while it remained high in those that progressed to chronicity. For both patients and chimpanzees, hepatic expression of IDO and CTLA-4 correlated directly. Induction of IDO may dampen T-cell reactivity to viral antigens in chronic HCV infection.
Larrea
Esther
E
Division of Gene Therapy and Hepatology, Center for Applied Medical Research, CIMA, Avenida Pío XII 55, 31008 Pamplona, Spain.
Riezu-Boj
José I
JI
Gil-Guerrero
Lucía
L
Casares
Noelia
N
Aldabe
Rafael
R
Sarobe
Pablo
P
Civeira
María P
MP
Heeney
Jonathan L
JL
Rollier
Christine
C
Verstrepen
Babs
B
Wakita
Takaji
T
Borrás-Cuesta
Francisco
F
Lasarte
Juan J
JJ
Prieto
Jesús
J
D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D060908:CTLA-4 Antigen; D015331:Cohort Studies; D015971:Gene Expression Regulation, Enzymologic; D006526:Hepatitis C / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000821:virology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger