The absence of IDO upregulates type I IFN production, resulting in suppression of viral replication in the retrovirus-infected mouse.
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.
Hoshi
Masato
M
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu City, Gifu Prefecture, Japan.
Saito
Kuniaki
K
Hara
Akira
A
Taguchi
Ayako
A
Ohtaki
Hirofumi
H
Tanaka
Ryo
R
Fujigaki
Hidetsugu
H
Osawa
Yosuke
Y
Takemura
Masao
M
Matsunami
Hidetoshi
H
Ito
Hiroyasu
H
Seishima
Mitsuru
M
D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000172:deficiency* / Q000235:genetics; D007370:Interferon Type I / Q000096:biosynthesis* / Q000502:physiology; D009052:Leukemia Virus, Murine / Q000254:growth & development / Q000276:immunology*; D007942:Leukemia, Experimental / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012192:Retroviridae Infections / Q000201:enzymology* / Q000276:immunology / Q000517:prevention & control*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014412:Tumor Virus Infections / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007370:Interferon Type I