AUTHOR=Albareda María C. , Natale María A. , De Rissio Ana M. , Fernandez Marisa , Serjan Alicia , Alvarez María G. , Cooley Gretchen , Shen Huifeng , Viotti Rodolfo , Bua Jacqueline , Castro Eiro Melisa D. , Nuñez Myriam , Fichera Laura E. , Lococo Bruno , Scollo Karenina , Tarleton Rick L. , Laucella Susana A. 

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

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01958

DOI=10.3389/fimmu.2018.01958

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> In contrast to adults, <italic>Trypanosoma cruzi</italic>-infected children have more broadly functional <italic>Trypanosoma cruzi</italic>-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.</p><p><bold>Methods:</bold> Using cytokine enzyme-linked immunosorbent spot (ELISPOT) polychromatic flow cytometry, cytometric bead assay, multiplex serological assays and quantitative PCR, we evaluated <italic>T. cruzi</italic>-specific T-cell and antibody immune responses, T-cell phenotypes and parasitemia in children in the early chronic phase of Chagas disease undergoing anti-<italic>Trypanosoma cruzi</italic> treatment.</p><p><bold>Results:</bold> Treatment with benznidazole or nifurtimox induced a decline in <italic>T. cruzi</italic>-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-<italic>T. cruzi</italic> 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<sup>+</sup>CD45RA<sup>−</sup>CCR7<sup>−</sup>CD62L<sup>−</sup> T cells prior to drug therapy was an independent indicator of successful treatment.</p><p><bold>Conclusions:</bold> 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.</p>