Increased activity of indoleamine 2,3-dioxygenase in serum from acutely infected dengue patients linked to gamma interferon antiviral function

Abstract

The depletion of L-tryptophan (L-Trp) has been associated with the inhibition of growth of microorganisms and also has profound effects on T cell proliferation and immune tolerance. The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses the rate-limiting step in the catabolic pathway of LTrp. Gene expression analysis has shown upregulation of genes involved in L-Trp catabolism in in vitro models of dengue virus (DENV) infection. To understand the role of IDO during DENV infection, we measured IDO activity in sera from control and DENV-infected patients. We found increased IDO activity, lower levels of L-Trp and higher levels of L-kynurenine in sera from DENVinfected patients during the febrile days of the disease compared with patients with other febrile illnesses and healthy donors. Furthermore, we confirmed upregulation of IDO mRNA expression in response to DENV infection in vitro, using a dendritic cell (DC) model of DENV infection. We found that the antiviral effect of gamma interferon (IFN-c) in DENV-infected DCs in vitro was partially dependent on IDO activity. Our results demonstrate that IDO plays an important role in the antiviral effect of IFN-c against DENV infection in vitro and suggest that it has a role in the immune response to DENV infections in vivo.

Role of indoleamine 2,3-dioxygenase in health and disease

“…Thus, IDO1 is up-regulated in vivo following infection with HSV-1 (herpes simplex virus type 1) [531], poliovirus (which causes poliomyelitis) [532], hepatitis C [533,534], dengue virus [535], Epstein-Barr virus (which causes glandular fever) [536], encephalomyocarditis virus (which causes encephalitis and myocarditis primarily in pigs) [537,538], LP-BM5 murine leukaemia virus (murine AIDS) [502], SIV (simian immunodeficiency virus) [539] and HIV [540][541][542][543].…”

The role of indoleamine 2, 3-dioxygenase in lepromatous leprosy immunosuppression

“…Unfortunately, sera IDO activity has only rarely been investigated in infectious diseases. In this connection, Becerra et al [47] found increased IDO activity in the sera of dengue virus (DENV)-infected patients during the most febrile days of the disease, indicating that IDO activity was at least partially dependent upon IFN-g.…”

Epstein-Barr Virus Infection Induces Indoleamine 2,3-Dioxygenase Expression in Human Monocyte-Derived Macrophages through p38/Mitogen-Activated Protein Kinase and NF-κB Pathways: Impairment in T Cell Functions

“…Infection with dengue virus, HIV, poliovirus, and hepatitis C virus is associated with IDO induction in various tissues and cell types, both in vivo and in vitro (19)(20)(21)(22). Previously reported evidence suggests that EBV infection increases the expression level of IDO in B cells and inhibits NK cell cytotoxicity (23).…”