Increased activity of indoleamine 2,3-dioxygenase in serum from acutely infected dengue patients linked to gamma interferon antiviral function.
The depletion of l-tryptophan (L-Trp) has been associated with the inhibition of growth of micro-organisms 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 L-Trp. 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 DENV-infected 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-gamma) 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-gamma against DENV infection in vitro and suggest that it has a role in the immune response to DENV infections in vivo.
Becerra
Aniuska
A
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Warke
Rajas V
RV
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Xhaja
Kris
K
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Evans
Barbara
B
University of Massachusetts Medical School Proteomic and Mass Spectrometry Core Facility, 365 Plantation Street, Worcester, MA 01605, USA.
Evans
James
J
University of Massachusetts Medical School Proteomic and Mass Spectrometry Core Facility, 365 Plantation Street, Worcester, MA 01605, USA.
Martin
Katherine
K
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
de Bosch
Norma
N
Banco Municipal de Sangre del Distrito Capital, San Jose, Caracas, Venezuela.
Rothman
Alan L
AL
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Bosch
Irene
I
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity*; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood*; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation; D055815:Young Adult
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma