The Significance of Discordant Serology in Chagas Disease: Enhanced T-Cell Immunity to Trypanosoma cruzi in Serodiscordant Subjects
BackgroundSubjects are considered infected with Trypanosoma cruzi 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 th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01141/full |
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| author | Melisa D. Castro Eiro María G. Alvarez Gretchen Cooley Rodolfo J. Viotti Graciela L. Bertocchi Bruno Lococo María C. Albareda Ana M. De Rissio María A. Natale Cecilia Parodi Rick L. Tarleton Susana A. Laucella Susana A. Laucella |
| author_facet | Melisa D. Castro Eiro María G. Alvarez Gretchen Cooley Rodolfo J. Viotti Graciela L. Bertocchi Bruno Lococo María C. Albareda Ana M. De Rissio María A. Natale Cecilia Parodi Rick L. Tarleton Susana A. Laucella Susana A. Laucella |
| author_sort | Melisa D. Castro Eiro |
| collection | DOAJ |
| description | BackgroundSubjects are considered infected with Trypanosoma cruzi 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.MethodsPeripheral blood mononuclear cells from SD and seropositive (SP) subjects, who were born in areas endemic for T. cruzi 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. T. cruzi-specific antibodies were quantified by conventional serology and a multiplex assay format.ResultsSD subjects exhibited immunity cell responses to T. cruzi 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 T. cruzi antigens and have a resting phenotype. SD individuals also have higher IFN-γ spot counts, polyfunctional CD4+ T-cells enriched in IL-2 secreting cells and low levels of antibodies specific for a set of T. cruzi-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 T. cruzi infection did not recognize Leishmania antigens.ConclusionBoth T-cell and humoral responses in most subjects assessed by conventional tests as SD for T. cruzi infection indicate prior exposure to infection and the establishment of immunological memory suggestive of a resolved infection. |
| first_indexed | 2024-12-19T10:01:07Z |
| format | Article |
| id | doaj.art-67683899e7df439d8b420b56b1474370 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T10:01:07Z |
| publishDate | 2017-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-67683899e7df439d8b420b56b14743702022-12-21T20:26:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-09-01810.3389/fimmu.2017.01141289611The Significance of Discordant Serology in Chagas Disease: Enhanced T-Cell Immunity to Trypanosoma cruzi in Serodiscordant SubjectsMelisa D. Castro Eiro0María G. Alvarez1Gretchen Cooley2Rodolfo J. Viotti3Graciela L. Bertocchi4Bruno Lococo5María C. Albareda6Ana M. De Rissio7María A. Natale8Cecilia Parodi9Rick L. Tarleton10Susana A. Laucella11Susana A. Laucella12Instituto Nacional de Parasitología ‘Dr. Mario Fatala Chabén’, Buenos Aires, ArgentinaHospital Interzonal General de Agudos Eva Perón, Buenos Aires, ArgentinaCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, United StatesHospital Interzonal General de Agudos Eva Perón, Buenos Aires, ArgentinaHospital Interzonal General de Agudos Eva Perón, Buenos Aires, ArgentinaHospital Interzonal General de Agudos Eva Perón, Buenos Aires, ArgentinaInstituto Nacional de Parasitología ‘Dr. Mario Fatala Chabén’, Buenos Aires, ArgentinaInstituto Nacional de Parasitología ‘Dr. Mario Fatala Chabén’, Buenos Aires, ArgentinaInstituto Nacional de Parasitología ‘Dr. Mario Fatala Chabén’, Buenos Aires, ArgentinaInstituto de Patología Experimental (CONICET), Universidad Nacional de Salta, Salta, ArgentinaCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, United StatesInstituto Nacional de Parasitología ‘Dr. Mario Fatala Chabén’, Buenos Aires, ArgentinaHospital Interzonal General de Agudos Eva Perón, Buenos Aires, ArgentinaBackgroundSubjects are considered infected with Trypanosoma cruzi 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.MethodsPeripheral blood mononuclear cells from SD and seropositive (SP) subjects, who were born in areas endemic for T. cruzi 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. T. cruzi-specific antibodies were quantified by conventional serology and a multiplex assay format.ResultsSD subjects exhibited immunity cell responses to T. cruzi 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 T. cruzi antigens and have a resting phenotype. SD individuals also have higher IFN-γ spot counts, polyfunctional CD4+ T-cells enriched in IL-2 secreting cells and low levels of antibodies specific for a set of T. cruzi-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 T. cruzi infection did not recognize Leishmania antigens.ConclusionBoth T-cell and humoral responses in most subjects assessed by conventional tests as SD for T. cruzi infection indicate prior exposure to infection and the establishment of immunological memory suggestive of a resolved infection.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01141/fullTrypanosoma cruziserodiscordanceT cellsmultiplex assaypolyfunctionality |
| spellingShingle | Melisa D. Castro Eiro María G. Alvarez Gretchen Cooley Rodolfo J. Viotti Graciela L. Bertocchi Bruno Lococo María C. Albareda Ana M. De Rissio María A. Natale Cecilia Parodi Rick L. Tarleton Susana A. Laucella Susana A. Laucella The Significance of Discordant Serology in Chagas Disease: Enhanced T-Cell Immunity to Trypanosoma cruzi in Serodiscordant Subjects Frontiers in Immunology Trypanosoma cruzi serodiscordance T cells multiplex assay polyfunctionality |
| title | The Significance of Discordant Serology in Chagas Disease: Enhanced T-Cell Immunity to Trypanosoma cruzi in Serodiscordant Subjects |
| title_full | The Significance of Discordant Serology in Chagas Disease: Enhanced T-Cell Immunity to Trypanosoma cruzi in Serodiscordant Subjects |
| title_fullStr | The Significance of Discordant Serology in Chagas Disease: Enhanced T-Cell Immunity to Trypanosoma cruzi in Serodiscordant Subjects |
| title_full_unstemmed | The Significance of Discordant Serology in Chagas Disease: Enhanced T-Cell Immunity to Trypanosoma cruzi in Serodiscordant Subjects |
| title_short | The Significance of Discordant Serology in Chagas Disease: Enhanced T-Cell Immunity to Trypanosoma cruzi in Serodiscordant Subjects |
| title_sort | significance of discordant serology in chagas disease enhanced t cell immunity to trypanosoma cruzi in serodiscordant subjects |
| topic | Trypanosoma cruzi serodiscordance T cells multiplex assay polyfunctionality |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01141/full |
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