<scp>l</scp>-Tryptophan-<scp>l</scp>-Kynurenine Pathway Metabolism Accelerated by<i>Toxoplasma</i><i>gondii</i>Infection Is Abolished in Gamma Interferon-Gene-Deficient Mice: Cross-Regulation between Inducible Nitric Oxide Synthase and Indoleamine-2,3-Dioxygenase

Fujigaki, Suwako; Saito, Kuniaki; Takemura, Masao; Maekawa, Naoya; Yamada, Yasuhiro; Wada, Hisayasu; Seishima, Mitsuru

doi:10.1128/iai.70.2.779-786.2002

Cited by 135 publications

(124 citation statements)

References 43 publications

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“…IDO and/or TDO both deplete the cellular microenvironment of trp and lead to the accumulation of trp metabolites. The evidence for immunomodulatory functions of trp catabolites is strong (25,26); the demonstration of a similar effect of trp deprivation has been more difficult to establish (27). The activation of the IDO pathway seems to impact on both T cells and DCs.…”

Section: Immune Tolerance Induction Through Trp Starvation and Trp Mementioning

confidence: 99%

The indoleamine 2,3‐dioxygenase (IDO) pathway controls allergy

Bubnoff

Bieber

2012

Allergy

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A series of recent studies have demonstrated that the immunoregulatory pathway of tryptophan catabolism, initiated by the enzyme indoleamine 2,3-dioxygenase (IDO), is a critical participant in allergic inflammation. Originally known for its regulatory function during pregnancy and during chronic inflammation in tumorigenesis and infection, the activity of IDO seems to positively modify the inflammatory state of atopy or allergy. The tryptophan degradation pathway is important for tolerance induction during systemic allergen immunotherapy. Here, we focus on recent findings that establish the IDO pathway as central to allergic inflammation.The indoleamine 2,3-dioxygenase (IDO) pathway has been found to contribute substantially to the control of allergic inflammation. Traditionally recognized for its immunomodulatory role in infection, pregnancy, autoimmunity, and neoplasia, the effect of IDO on allergy appears to be a another piece of puzzle in the 'hygiene hypothesis'. Early microbial exposure and thus the stimulation of the IDO pathway by distinct Toll-like receptors (TLR) may, together with other immunoregulatory pathways, shape the predisposition to and determine the outcome of allergic inflammation, autoimmunity, and probably other diseases. Current data suggest that a normal induction of IDO activity, which decreases serum tryptophan (trp) levels and increases the levels of trp metabolites, controls the allergic inflammation. The mechanism of IDO-induced tolerance induction can probably be manifold but the induction of regulatory T cells may be a major aspect of the control function over allergic inflammation. This review summarizes the current knowledge on the IDO pathway and its role in regulating immune functions with a focus on allergic diseases.Tryptophan and its degradation pathways: indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase (TDO)As an essential amino acid, tryptophan (trp) is a constituent of proteins. Inadequate dietary intake of trp and other essential amino acids can lead to a negative nitrogen balance and to a loss of muscle mass, brain size, and weight (1). Trp is an essential starting point of two biochemical pathways: (i) the enzyme tryptophan 5-hydroxylase converts trp into 5-hydroxytryptophan, which is subsequently decarboxylized to 5-hydroxytryptamine (5-HT, serotonin), an essential neurotransmitter and vasoconstrictor, and (ii) two atoms of the molecular oxygen are inserted into L-trp to form N-formylkynurenine, the first and rate-limiting step in the kynurenine pathway (Fig. 1) (2, 3). The activation of molecular oxygen and its insertion into trp are catalyzed by three

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Section: Immune Tolerance Induction Through Trp Starvation and Trp Mementioning

confidence: 99%

The indoleamine 2,3‐dioxygenase (IDO) pathway controls allergy

Bubnoff

Bieber

2012

Allergy

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“…IDO activity was assayed as described in a previous report (13). In brief, tissues were homogenized with a Polytron homogenizer (Kinematica, Lucerne, Switzerland) in 1.5 volumes of ice-cold 0.14 M KCl-20 mM potassium phosphate buffer (pH 7).…”

Section: Enzymatic Assay For Ido Activitymentioning

confidence: 99%

“…Parasites were harvested from the brains of mice chronically infected with T. gondii cysts ("Fukaya" strain) as described in a previous report (13). Brain tissue was dispersed in saline.…”

Section: Toxoplasma Gondii Infectionmentioning

confidence: 99%

“…cDNA quantification for IDO, b-actin, IL-4, IL-10, TGF-b, 18s, IFN-a, -b, and Foxp3 was performed using real-time PCR conducted with LightCycler (Roche, Meylan, France). IDO, IFN-a, and b-actin reactions were performed using a SYBR green PCR mix (Qiagen, Hilden, Germany) as described in a previous report (13). IL-4, IL-10, TGF-b, 18s, IFN-b, and Foxp3 reactions were performed using a TaqMan probe.…”

Section: Rna Extraction Rt-pcr and Real-time Pcrmentioning

confidence: 99%

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

Hoshi¹,

Saito

Hara

et al. 2010

The Journal of Immunology

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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.

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“…12 All immunologic mechanisms involved have not yet been unraveled, but it is known that interferon-gamma (IFN-c) and the enzyme indoleamine 2,3-dioxygenase (IDO) play a role. [13][14][15][16][17] Activated Thelper cells secrete IFN-c, which induces IDO. This enzyme degrades the tryptophan that is needed for the tachyzoitic phase of TG.…”

Section: Introductionmentioning

confidence: 99%

A controlled prospective study of Toxoplasma gondii infection in individuals with schizophrenia: Beyond seroprevalence

et al. 2007

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Toxoplasma gondii (TG) infection has been reported to be more frequent in schizophrenia. The interaction of the lifelong persisting parasite with the host's immune system involves T-cell/interferon-gamma-induced degradation of tryptophan and provides a challenge to the host well beyond a possible role in the etiology of schizophrenia. The hypothesis we tested in this study was that TG infection may be more frequent (serofrequency) and/or more intense (serointensity) in patients with schizophrenia or major depression compared with psychiatrically healthy controls. In addition, these measures are associated with the clinical course. We did a cross-sectional, prospective investigation of individuals with schizophrenia (n = 277) and major depression (n = 465) admitted to our department (2002)(2003)(2004)(2005) and of healthy controls (n = 214), with all groups adjusted for age and geographic home region. Serofrequency was comparable between the groups, but serointensity was significantly higher in the patients. In individuals with schizophrenia, serointensity was significantly positively associated with C-reactive protein levels and leukocyte counts, and firstepisode patients yielded significantly higher serotiters. Immunomodulatory medication was associated with decreased serotiters. In addition, the route of infection appears to differ between patients and controls. Thus, our results support increased host responses to TG infection in the patients, as well as increased titers in first-episode patients with schizophrenia; this may relate to the shifted T-helper 1/2 status described in these patients. Therefore, we suggest that TG infection, particularly in individuals with schizophrenia, is an important environmental factor in the interaction between psychiatric vulnerability, genetic background, immunomodulation, and the neurotransmitter systems.

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l-Tryptophan-l-Kynurenine Pathway Metabolism Accelerated byToxoplasmagondiiInfection Is Abolished in Gamma Interferon-Gene-Deficient Mice: Cross-Regulation between Inducible Nitric Oxide Synthase and Indoleamine-2,3-Dioxygenase

Cited by 135 publications

References 43 publications

The indoleamine 2,3‐dioxygenase (IDO) pathway controls allergy

The indoleamine 2,3‐dioxygenase (IDO) pathway controls allergy

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

A controlled prospective study of Toxoplasma gondii infection in individuals with schizophrenia: Beyond seroprevalence

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