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2015 ; 180
(3
): 484-98
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Indolamine 2,3-dioxygenase expression by monocytes and dendritic cell populations
in hepatitis C patients
#MMPMID25605587
Schulz S
; Landi A
; Garg R
; Wilson JA
; van Drunen Littel-van den Hurk S
Clin Exp Immunol
2015[Jun]; 180
(3
): 484-98
PMID25605587
show ga
Dendritic cells (DCs) play an important role in the induction of the primary
immune response to infection. DCs may express the tryptophan-catabolizing enzyme
indolamine2,3-dioxygenase (IDO), which is an inducer of immune tolerance. Because
there is evidence that chronic hepatitis C virus (HCV) infection leads to
functional impairment of certain DC populations, we analysed IDO expression in
DCs and monocytes from chronically infected and recovered HCV patients. The IDO1
and -2 expression was increased significantly in the monocytes of chronic HCV
patients but, interestingly, not in those from recovered patients. The myeloid
DCs from chronically infected HCV patients also showed enhanced IDO1 expression,
while no change in either IDO1 or -2 was found for plasmacytoid DCs.
Up-regulation of IDO1 gene expression was confirmed by the presence of enhanced
kynurenine/tryptophan ratios in the plasma from chronic HCV patients. Increased
IDO1 and -2 expression was also observed in monocytes from healthy donors
infected with an adapted mutant of the HCV JFH-1 strain ex vivo, confirming a
direct effect of HCV infection. These changes in IDO expression could be
prevented by treatment with the IDO inhibitor 1-methyl tryptophan (1-mT).
Furthermore, maturation of monocyte-derived DCs from chronically infected HCV
patients, as well as well as monocyte-derived DCs infected ex vivo with HCV, was
impaired, but this was reversed by 1-mT treatment. This suggests that IDO
inhibitors may be used to treat chronic HCV patients in vivo, in conjunction with
current therapies, or to activate DCs from patients ex vivo, such that they can
be administered back as a DC-based therapeutic vaccine.