%A Albareda,María C. %A Natale,María A. %A De Rissio,Ana M. %A Fernandez,Marisa %A Serjan,Alicia %A Alvarez,María G. %A Cooley,Gretchen %A Shen,Huifeng %A Viotti,Rodolfo %A Bua,Jacqueline %A Castro Eiro,Melisa D. %A Nuñez,Myriam %A Fichera,Laura E. %A Lococo,Bruno %A Scollo,Karenina %A Tarleton,Rick L. %A Laucella,Susana A. %D 2018 %J Frontiers in Immunology %C %F %G English %K Trypanosoma cruzi,T cells,Benznidazole,Nifurtimox,Pediatric infectious diseases %Q %R 10.3389/fimmu.2018.01958 %W %L %M %P %7 %8 2018-September-13 %9 Original Research %# %! Immune markers in anti-T.cruzi treatment outcomes %* %< %T Distinct Treatment Outcomes of Antiparasitic Therapy in Trypanosoma cruzi-Infected Children Is Associated With Early Changes in Cytokines, Chemokines, and T-Cell Phenotypes %U https://www.frontiersin.org/articles/10.3389/fimmu.2018.01958 %V 9 %0 JOURNAL ARTICLE %@ 1664-3224 %X 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 5-year follow-up study. A multivariate analysis demonstrated that lower frequency of CD4+CD45RACCR7CD62L T cells prior to drug therapy was an independent indicator of successful treatment.Conclusions: These findings further validate the usefulness of alternative metrics to monitor treatment outcomes. Distinct qualitative and quantitative characteristics of T cells prior to drug therapy may be linked to treatment efficacy.