AUTHOR=Castro Eiro Melisa D. , Alvarez María G. , Cooley Gretchen , Viotti Rodolfo J. , Bertocchi Graciela L. , Lococo Bruno , Albareda María C. , De Rissio Ana M. , Natale María A. , Parodi Cecilia , Tarleton Rick L. , Laucella Susana A. 

TITLE=The Significance of Discordant Serology in Chagas Disease: Enhanced T-Cell Immunity to Trypanosoma cruzi in Serodiscordant Subjects

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01141

DOI=10.3389/fimmu.2017.01141

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Background</title><p>Subjects are considered infected with <italic>Trypanosoma cruzi</italic> when tested positive by at least two out of three serological tests, whereas a positive result in only one of up to three tests is termed “serodiscordant” (SD). Assessment of parasite-specific T-cell responses may help discriminate the uninfected from infected individuals among SD subjects.</p></sec><sec id="ST2"><title>Methods</title><p>Peripheral blood mononuclear cells from SD and seropositive (SP) subjects, who were born in areas endemic for <italic>T. cruzi</italic> infection but living in Buenos Aires city, Argentina, at the time of the study, and seronegative unexposed subjects were included for analysis. The function and phenotype of T cells were assessed by interferon-γ (IFN-γ) and interleukin (IL)-2 enzyme-linked immunospot assay and multiparameter flow cytometry. <italic>T. cruzi</italic>-specific antibodies were quantified by conventional serology and a multiplex assay format.</p></sec><sec id="ST3"><title>Results</title><p>SD subjects exhibited immunity cell responses to <italic>T. cruzi</italic> but in contrast to SP subjects, T cells in SD subjects more often display the simultaneous production of IFN-γ and IL-2 in response to <italic>T. cruzi</italic> antigens and have a resting phenotype. SD individuals also have higher IFN-γ spot counts, polyfunctional CD4<sup>+</sup> T-cells enriched in IL-2 secreting cells and low levels of antibodies specific for a set of <italic>T. cruzi</italic>-derived recombinant proteins compared with the SP group. Long-term follow-up of SD individuals confirmed that humoral and T-cell responses fluctuate but are sustained over time in these subjects. T cells in SD subjects for <italic>T. cruzi</italic> infection did not recognize <italic>Leishmania</italic> antigens.</p></sec><sec id="ST4"><title>Conclusion</title><p>Both T-cell and humoral responses in most subjects assessed by conventional tests as SD for <italic>T. cruzi</italic> infection indicate prior exposure to infection and the establishment of immunological memory suggestive of a resolved infection.</p></sec>