IDO1-AhR axis increases T regulatory cells in Plasmodium vivax malaria infection

作者：Rafaella Oliveira dos Santos, Nani Oliveira Carvalho, Thiago Barros do Nascimento de Morais, Wlademir Braga Salgado Sobrinho, Maria Geuziane Soares da Cruz, Elaine Speziali de Faria, Fernanda Fortes de Araújo, Vanessa Peruhype-Magalhães, Stefanie Costa Pinto Lopes, Adriana Malheiros, Adolfo José da Mota, Helton C. Santiago, Paulo Afonso Nogueira, Andréa Teixeira‐Carvalho, Marcus Lacerda, Pritesh Lalwani · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1474447 · 被引用次数：4 · 研究领域：Tryptophan and brain disorders、Stress Responses and Cortisol、Bipolar Disorder and Treatment

Introduction Malaria remains a significant public health challenge in Brazil, where Plasmodium vivax ( P. vivax ) is the predominant species. Dysregulated immune responses contribute substantially to malaria pathogenesis. Indoleamine 2,3-dioxygenase (IDO) mediates the catabolism of tryptophan (TRP) into kynurenine (KYN), an immunosuppressive metabolite implicated in immune tolerance. This study aimed to investigate the role of TRP catabolism and regulatory T cells (Tregs) during P. vivax infection. Methods Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with P. vivax -infected erythrocyte (Pv-iE) lysate to assess IDO-1 expression, KYN/TRP ratio, cytokine production, and Treg frequency. The effects of pharmacological inhibition of IDO, MyD88, and aryl hydrocarbon receptor (AhR) pathways were evaluated. Additionally, plasma KYN/TRP ratio, Treg frequencies, and cytokine levels were measured in patients with acute P. vivax infection and compared between individuals experiencing their first malaria episode and those with previous infections. Results Stimulation with Pv-iE lysate increased IDO-1 expression in CD14 + cells, elevated KYN/TRP ratio, and induced pro-inflammatory cytokine production. IDO inhibition reduced KYN/TRP ratio and Treg frequencies upon Pv-iE stimulation. MyD88 inhibition decreased both IDO-1 expression and KYN/TRP ratio. IDO and AhR inhibition reduced Treg frequencies and CD4 + T cell proliferation. Patients with acute P. vivax malaria exhi...