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

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]

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

• 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
• Modalidade de apoio: Auxílio à Pesquisa - Regular