%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+CD45RA−CCR7−CD62L− 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.