Distinct Treatment Outcomes of Antiparasitic Therapy in Trypanosoma cruzi-Infected Children Is Associated With Early Changes in Cytokines, Chemokines, and T-Cell Phenotypes

作者：María C. Albareda, María A. Natale, Ana M. De Rissio, Marisa Fernández, Alicia Serjan, M Alvarez, Gretchen Cooley, Huifeng Shen, Rodolfo Viotti, Jacqueline Búa, Melisa D. Castro Eiro, Myriam Núñez, Laura E. Fichera, Bruno Lococo, Karenina Scollo, Rick L. Tarleton, Susana A. Laucella · 发表于：Frontiers in Immunology · 年份：2018 · DOI：10.3389/fimmu.2018.01958 · 被引用次数：33 · 研究领域：Trypanosoma species research and implications、Research on Leishmaniasis Studies、Parasites and Host Interactions

Background. In contrast to adults, Trypanosoma cruzi-infected children have more broadly functional Trypanosoma cruzi-specific T cells, and the total T-cell compartment exhibits fewer signs of immune exhaustion. However, not much is known about the link between immunocompetence and the treatment efficacy for human Chagas disease. Methods. Using cytokine enzyme-linked immunosorbent spot (ELISPOT) polychromatic flow cytometry, cytometric bead assay, multiplex serological assays and quantitative PCR, we evaluated T. cruzi-specific T-cell and antibody immune responses, T-cell phenotypes and parasitemia in children in the early chronic phase of Chagas disease undergoing anti-Trypanosoma cruzi treatment. Results. Treatment with benznidazole or nifurtimox induced a decline in T. cruzi-specific IFN-γ- and IL-2-producing cells and proinflammatory cytokines and chemokines. T-cell responses became detectable after therapy in children bearing T-cell responses under background levels prior to treatment. The total frequencies of effector, activated and antigen-experienced T cells also decreased following anti-T. cruzi therapy, along with an increase in T cells expressing the receptor of the homeostatic cytokine IL-7. Posttreatment changes in several of these markers distinguished children with a declining serologic response suggestive of successful treatment from those with sustained serological responses in a five-year follow-up study. A multivariate analysis demonstrated that lower frequ...