Kynurenine elevation correlates with T regulatory cells increase in acute Plasmodium vivax infection: A pilot study

Background Disease‐tolerance mechanisms limit infection severity by preventing tissue damage; however, the underlying mechanisms in human malaria are still unclear. Tryptophan (TRP), an essential amino acid, is catabolized into tolerogenic metabolites, kynurenines (KYN), by indoleamine 2,3‐dioxygena...

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Bibliographic Details
Published in:Parasite immunology 2020-03, Vol.42 (3), p.e12689-n/a
Main Authors: Santos, Rafaella Oliveira, Gonçalves‐Lopes, Raquel M., Lima, Nathália F., Scopel, Kézia K. G., Ferreira, Marcelo U., Lalwani, Pritesh
Format: Article
Language:English
Subjects:
Amino acids
Cytokines
Dioxygenase
Flow cytometry
Foxp3 protein
High-performance liquid chromatography
Immunoregulation
Infections
inflammation
Interferon
kynurenine
Lymphocytes T
Malaria
Metabolites
Plasmodium
T regulatory cells and immunosuppression
Tryptophan
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Summary:Background Disease‐tolerance mechanisms limit infection severity by preventing tissue damage; however, the underlying mechanisms in human malaria are still unclear. Tryptophan (TRP), an essential amino acid, is catabolized into tolerogenic metabolites, kynurenines (KYN), by indoleamine 2,3‐dioxygenase 1 (IDO1), which can induce Foxp3+ T regulatory cells (Tregs). In this study, we evaluated the relationship of these metabolites with Treg‐mediated tolerance induction in acute malaria infections. Methods We performed a cross‐sectional study that evaluated asymptomatic, symptomatic malaria patients and endemic control patient groups. We assessed plasmatic concentration of cytokines by ELISA. Plasmatic TRP and KYN levels were measured by HPLC. Peripheral T regulatory cells were measured and phenotyped by flow cytometry. Results The KYN/TRP ratio was significantly elevated in asymptomatic and symptomatic Plasmodium infection, compared to healthy controls. Also, Th1 and Th2 cytokines were elevated in the acute phase of malaria disease. IFN‐γ increase in acute phase was positively correlated with the KYN/TRP ratio and KYN elevation was positively correlated with the increase of peripheral FoxP3+ T regulatory cells. Conclusions Additional studies are needed not only to identify innate mechanisms that increase tryptophan catabolism but also the role of Tregs in controlling malaria‐induced pathology and malaria tolerance by the host.
ISSN:0141-9838
1365-3024
DOI:10.1111/pim.12689