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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
dos Santos, Rafaella Oliveira [1] ; Goncalves-Lopes, Raquel M. [2, 3] ; Lima, Nathalia F. [2, 4] ; Scopel, Kezia K. G. [5] ; Ferreira, Marcelo U. [2] ; Lalwani, Pritesh [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Fiocruz Amazonia, ILMD, Manaus, Amazonas - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil
[3] Univ Estadual Campinas, Hemoctr Campinas, UNICAMP, Campinas, SP - Brazil
[4] Heidelberg Univ, Ctr Infect Dis, Parasitol Unit, Med Sch, Heidelberg - Germany
[5] Univ Fed Juiz de Fora, Inst Biol Sci, Dept Parasitol Microbiol & Immunol, Juiz De Fora - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: PARASITE IMMUNOLOGY; v. 42, n. 3 JAN 2020.
Citações Web of Science: 0
Resumo

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-gamma 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. (AU)

Processo FAPESP: 10/52146-0 - Caracterização fenotípica e funcional de populações de linfócitos T CD4+ com possível função imunorreguladora na malária humana
Beneficiário:Marcelo Urbano Ferreira
Linha de fomento: Auxílio à Pesquisa - Regular