Inhibition of increased indoleamine 2,3-dioxygenase activity attenuates Toxoplasma gondii replication in the lung during acute infection

Yuki Murakami, Masato Hoshi, Akira Hara, Masao Takemura, Yuko Arioka, Yasuko Yamamoto, Hidetoshi Matsunami, Tadao Funato, Mitsuru Seishima, Kuniaki Saito

研究成果: Article

20 引用 (Scopus)

抄録

The regulation of local l-tryptophan concentrations by tryptophan-degrading enzyme, indoleamine 2,3-dioxygenase (IDO) induced by various stimuli such as interferon-γ (IFN-γ) is one of the key mechanisms in antimicrobial effect. Recently, IDO is also focused on an immunosuppressive mechanism shared by several different immune cell types. Here, we show that inhibition of increased IDO activity maybe involved in the antiparasitic mechanism during Toxoplasma gondii (T. gondii) infection in vivo. In this study, we investigated the role of IDO by using IDO-gene-deficient (IDO KO) mice and by administering a competitive enzyme inhibitor, 1-methyl- d,. l-tryptophan (1MT), to wild-type mice following T. gondii infection. Although depletion of lung l-tryptophan did not occur in IDO KO mice after T. gondii infection, the increased mRNA expression of T. gondii surface antigen gene 2 (SAG2) and the inflammatory cytokines in the lung were drastically reduced in the IDO KO mice following infection. We also found that complete depletion of lung l-tryptophan was observed in wild-type mice after infection, but not in mice treated with 1MT. At the same time, 1MT suppressed the increased mRNA expression of SAG2. Taken together, we observed that the inflammatory damage was significantly decreased by the administration of 1MT in the lung after infection. Inhibition of the IDO activity or the elimination of IDO's substrate may be an effective therapy against microbial diseases.

元の言語English
ページ(範囲)245-251
ページ数7
ジャーナルCytokine
59
発行部数2
DOI
出版物ステータスPublished - 01-08-2012
外部発表Yes

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Toxoplasma
Lung
Tryptophan
Infection
Toxoplasmosis
Genes
Surface Antigens
Antiparasitic Agents
Messenger RNA
Enzyme Inhibitors
Immunosuppressive Agents
Interferons
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

これを引用

Murakami, Yuki ; Hoshi, Masato ; Hara, Akira ; Takemura, Masao ; Arioka, Yuko ; Yamamoto, Yasuko ; Matsunami, Hidetoshi ; Funato, Tadao ; Seishima, Mitsuru ; Saito, Kuniaki. / Inhibition of increased indoleamine 2,3-dioxygenase activity attenuates Toxoplasma gondii replication in the lung during acute infection. :: Cytokine. 2012 ; 巻 59, 番号 2. pp. 245-251.
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abstract = "The regulation of local l-tryptophan concentrations by tryptophan-degrading enzyme, indoleamine 2,3-dioxygenase (IDO) induced by various stimuli such as interferon-γ (IFN-γ) is one of the key mechanisms in antimicrobial effect. Recently, IDO is also focused on an immunosuppressive mechanism shared by several different immune cell types. Here, we show that inhibition of increased IDO activity maybe involved in the antiparasitic mechanism during Toxoplasma gondii (T. gondii) infection in vivo. In this study, we investigated the role of IDO by using IDO-gene-deficient (IDO KO) mice and by administering a competitive enzyme inhibitor, 1-methyl- d,. l-tryptophan (1MT), to wild-type mice following T. gondii infection. Although depletion of lung l-tryptophan did not occur in IDO KO mice after T. gondii infection, the increased mRNA expression of T. gondii surface antigen gene 2 (SAG2) and the inflammatory cytokines in the lung were drastically reduced in the IDO KO mice following infection. We also found that complete depletion of lung l-tryptophan was observed in wild-type mice after infection, but not in mice treated with 1MT. At the same time, 1MT suppressed the increased mRNA expression of SAG2. Taken together, we observed that the inflammatory damage was significantly decreased by the administration of 1MT in the lung after infection. Inhibition of the IDO activity or the elimination of IDO's substrate may be an effective therapy against microbial diseases.",
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Inhibition of increased indoleamine 2,3-dioxygenase activity attenuates Toxoplasma gondii replication in the lung during acute infection. / Murakami, Yuki; Hoshi, Masato; Hara, Akira; Takemura, Masao; Arioka, Yuko; Yamamoto, Yasuko; Matsunami, Hidetoshi; Funato, Tadao; Seishima, Mitsuru; Saito, Kuniaki.

:: Cytokine, 巻 59, 番号 2, 01.08.2012, p. 245-251.

研究成果: Article

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AU - Murakami, Yuki

AU - Hoshi, Masato

AU - Hara, Akira

AU - Takemura, Masao

AU - Arioka, Yuko

AU - Yamamoto, Yasuko

AU - Matsunami, Hidetoshi

AU - Funato, Tadao

AU - Seishima, Mitsuru

AU - Saito, Kuniaki

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