The Absence of IDO Upregulates Type I IFN Production, Resulting in Suppression of Viral Replication in the Retrovirus-Infected Mouse

Abstract

Indoleamine 2,3-dioxygenase, the l-tryptophan–degrading enzyme, plays a key role in the powerful immunomodulatory effects on several different types of cells. Because modulation of IDO activities after viral infection may have great impact on disease progression, we investigated the role of IDO following infection with LP-BM5 murine leukemia virus. We found suppressed BM5 provirus copies and increased type I IFNs in the spleen from IDO knockout (IDO−/−) and 1-methyl-d-l-tryptophan–treated mice compared with those from wild-type (WT) mice. Additionally, the number of plasmacytoid dendritic cells in IDO−/− mice was higher in the former than in the WT mice. In addition, neutralization of type I IFNs in IDO−/− mice resulted in an increase in LP-BM5 viral replication. Moreover, the survival rate of IDO−/− mice or 1-methyl-d-l-tryptophan–treated mice infected with LP-BM5 alone or with both Toxoplasma gondii and LP-BM5 was clearly greater than the survival rate of WT mice. To our knowledge, the present study is the first report to observe suppressed virus replication with upregulated type I IFN in IDO−/− mice, suggesting that modulation of the IDO pathway may be an effective strategy for treatment of virus infection.

Apicomplexan Parasite, Eimeria falciformis, Co-opts Host Tryptophan Catabolism for Life Cycle Progression in Mouse

“…In contrast, inhibition or deficiency of enzyme during other parasitic (Leishmania donovani (18) and Trichuris muris (43)) and bacterial (Citrobacter rodentium (44)) infections reduced the pathogen burden in animals. Moreover, 1-MT, a competitive inhibitor of IDO, had none (herpes simplex virus 1) to a negative (BM5) influence on the virus replication in mice (18,45), which occasionally differs with in vitro findings (46). Likewise, IDO1 as a positive determinant of Eimeria growth does not reconcile with canonical antimicrobial function, notwithstanding a potential depletion of tryptophan in the infected host cell.…”

A STING-activating nanovaccine for cancer immunotherapy

“…Mice were intravenously injected with 30 μg pDNA mixed with in vivo -jetPEI (Polyplus -transfection, N:P =8) or were injected s.c. with NPs (150 μg, 5-fold of vaccine dose). IDO activity was measured as described in previous reports 40,41 . Enzyme activity was expressed as the product content per hour per gram of tissue protein.…”

Antigen-Specific Antitumor Responses Induced by OX40 Agonist Are Enhanced by the IDO Inhibitor Indoximod

“…The IDO enzymatic activity in tumor homogenates was assessed using high-performance liquid chromatography (HPLC) techniques as described earlier (48). Briefly, a concentration of kynurenine (tryptophan catabolite) was measured before and after 2 hours of addition of exogenous L-tryptophan substrate solution into tumor homogenates.…”