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Role of Kynurenine Pathway in Infections

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Targeting the Broadly Pathogenic Kynurenine Pathway

Abstract

Tryptophan is an essential amino acid, not only for mammals but also for a broad range of pathogens. The majority of the dietary tryptophan is degraded via the kynurenine pathway to kynurenine and other downstream tryptophan metabolites, together termed “kynurenines”. The induction of the kynurenine pathway in the context of infections is currently the focus of many human and mouse studies. It has been shown that infections with viruses, parasites and bacteria result in a reduction in tryptophan levels and enhanced levels of kynurenines in the plasma/serum and cerebrospinal fluid. These changes influence the survival of pathogens and the activity of the immune system, respectively. On the one hand, low levels of tryptophan mediate antimicrobial effects through tryptophan starvation but also inhibit an adequate immune defence. On the other hand kynurenines exert toxic effects on both pathogens and the cellular immune system. The interplay of all these antimicrobial and immunoregulatory effects of kynurenines is the focus of this chapter.

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Abbreviations

1-MT:

1-Methyl tryptophan

3-HK:

3-Hydroxykynurenine

3-HAA:

3-Hydroxyanthranilic acid

CSF:

Cerebrospinal fluid

DCs:

Dendritic cells

IC50 :

Half maximal inhibitory concentrations

IDO:

Indoleamine 2,3-dioxygenase

IDO-2:

Indoleamine 2,3-dioxygenase-2

IFN-γ:

Interferon-γ

KYN:

Kynurenine

Mtb:

Mycobacterium tuberculosis

NO:

Nitric oxide

PA:

Picolinic acid

QUIN:

Quinolinic acid

TDO:

Tryptophan 2,3-dioxygenase

TRP:

Tryptophan

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Acknowledgements

We thank Dr. T. Bruhn for critical proofreading of the manuscript. The study was supported by German Research Council (DFG) Grant no. RU729 and the Graduate School “Molecules of Infection” Manchot Foundation.

Disclosures

The authors report no conflicting financial interests.

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Authors and Affiliations

  1. Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine University, Universitätsstrasse 1, 40225, Düsseldorf, Germany

    Silvia Kathrin Eller & Walter Däubener

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  1. Silvia Kathrin Eller
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  2. Walter Däubener
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Correspondence to Walter Däubener .

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Editors and Affiliations

  1. Chairman, Department of Neurosurgery, Wayne State University, Detroit, Michigan, USA

    Sandeep Mittal

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Eller, S.K., Däubener, W. (2015). Role of Kynurenine Pathway in Infections. In: Mittal, S. (eds) Targeting the Broadly Pathogenic Kynurenine Pathway. Springer, Cham. https://doi.org/10.1007/978-3-319-11870-3_14

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