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Role of Kynurenine Pathway in HIV/AIDS

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Targeting the Broadly Pathogenic Kynurenine Pathway

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Abstract

Two of the most fundamental requirements for the host are the ability to survive periods of starvation and the capacity to mount an effective response against pathogenic invaders while tolerating mucosa-associated commensal microbes. The kynurenine (Kyn) pathway (KP) is at the crossroad of these two fundamental requirements and therefore plays an important role in HIV infection. The combination of HIV infection and tryptophan catalytic bacteria causes CD4 Th17/Th22 dysfunction in the gut mucosa leading to microbial translocation that creates a systemic KP activation cycle. This self-sustaining feedback loop has deleterious effects on disease progression and on neurocognitive impairment in HIV-infected patients while fuelling a systemic state of immune activation.

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Abbreviations

AhR:

Aryl hydrocarbon receptor

AIDS:

Acquired immune deficiency syndrome

ART:

Antiretroviral therapy

CSF:

Cerebrospinal fluid

CRP:

C-reactive protein

HAND:

HIV-associated neurocognitive disorder

HIV:

Human immunodeficiency virus

IAld:

Indole-3-aldehyde

IDO:

Indoleamine 2,3-dioxygenase

I-FABP:

Intestinal fatty acid-binding protein

IFN:

Interferon

IL:

Interleukin

KP:

Kynurenine pathway

Kyn:

Kynurenine

NK:

Natural killer cells

sCD14:

Soluble CD14

Treg:

Regulatory T cells

Trp:

Tryptophan

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Acknowledgements

The authors acknowledge Angie Massicotte and Dr. Wei Cao for coordination and assistance. This work was supported by the Canadian Institutes of Health Research (grant MOP #103230 and CTN #257) and Fonds de la Recherche Québec-Santé (FRQ-S): Thérapie cellulaire and Réseau SIDA/Maladies infectieuses, Québec, Canada. Dr. Vikram Mehraj is supported by FRQ-S postdoctoral fellowship award. Dr. Jean-Pierre Routy is a holder of Louis Lowenstein Chair in Hematology and Oncology, McGill University.

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Authors and Affiliations

  1. Division of Hematology, McGill University Health Centre, Montreal, QC, Canada

    Jean-Pierre Routy

  2. Chronic Viral Illness Service, McGill University Health Centre, Glen site, 1001 Boulevard Décarie, EM 3-3232, Montreal, QC, Canada, H4A 3J1

    Jean-Pierre Routy, Vikram Mehraj & Kishanda Vyboh

  3. Research Institute of the McGill University Health Centre, Montreal, QC, Canada

    Jean-Pierre Routy, Vikram Mehraj & Kishanda Vyboh

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  1. Jean-Pierre Routy
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  2. Vikram Mehraj
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Correspondence to Jean-Pierre Routy .

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

    Sandeep Mittal

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Routy, JP., Mehraj, V., Vyboh, K. (2015). Role of Kynurenine Pathway in HIV/AIDS. In: Mittal, S. (eds) Targeting the Broadly Pathogenic Kynurenine Pathway. Springer, Cham. https://doi.org/10.1007/978-3-319-11870-3_9

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