Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell Immunity
While it is now acknowledged that CD4+ T cells expressing CD25 and Foxp3 (Treg cells) regulate immune responses and, consequently, influence the pathogenesis of infectious diseases, the regulatory response mediated by Treg cells upon infection by Trypanosoma cruzi was still poorly characterized. In...
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| Format: | Article |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02555/full |
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| author | Cintia L. Araujo Furlan Cintia L. Araujo Furlan Jimena Tosello Boari Jimena Tosello Boari Constanza Rodriguez Constanza Rodriguez Fernando P. Canale Fernando P. Canale Facundo Fiocca Vernengo Facundo Fiocca Vernengo Santiago Boccardo Santiago Boccardo Cristian G. Beccaria Cristian G. Beccaria Véronique Adoue Véronique Adoue Véronique Adoue Olivier Joffre Olivier Joffre Olivier Joffre Adriana Gruppi Adriana Gruppi Carolina L. Montes Carolina L. Montes Eva V. Acosta Rodriguez Eva V. Acosta Rodriguez |
| author_facet | Cintia L. Araujo Furlan Cintia L. Araujo Furlan Jimena Tosello Boari Jimena Tosello Boari Constanza Rodriguez Constanza Rodriguez Fernando P. Canale Fernando P. Canale Facundo Fiocca Vernengo Facundo Fiocca Vernengo Santiago Boccardo Santiago Boccardo Cristian G. Beccaria Cristian G. Beccaria Véronique Adoue Véronique Adoue Véronique Adoue Olivier Joffre Olivier Joffre Olivier Joffre Adriana Gruppi Adriana Gruppi Carolina L. Montes Carolina L. Montes Eva V. Acosta Rodriguez Eva V. Acosta Rodriguez |
| author_sort | Cintia L. Araujo Furlan |
| collection | DOAJ |
| description | While it is now acknowledged that CD4+ T cells expressing CD25 and Foxp3 (Treg cells) regulate immune responses and, consequently, influence the pathogenesis of infectious diseases, the regulatory response mediated by Treg cells upon infection by Trypanosoma cruzi was still poorly characterized. In order to understand the role of Treg cells during infection by this protozoan parasite, we determined in time and space the magnitude of the regulatory response and the phenotypic, functional and transcriptional features of the Treg cell population in infected mice. Contrary to the accumulation of Treg cells reported in most chronic infections in mice and humans, experimental T. cruzi infection was characterized by sustained numbers but decreased relative frequency of Treg cells. The reduction in Treg cell frequency resulted from a massive accumulation of effector immune cells, and inversely correlated with the magnitude of the effector immune response as well as with emergence of acute immunopathology. In order to understand the causes underlying the marked reduction in Treg cell frequency, we evaluated the dynamics of the Treg cell population and found a low proliferation rate and limited accrual of peripheral Treg cells during infection. We also observed that Treg cells became activated and acquired a phenotypic and transcriptional profile consistent with suppression of type 1 inflammatory responses. To assess the biological relevance of the relative reduction in Treg cells frequency observed during T. cruzi infection, we transferred in vitro differentiated Treg cells at early moments, when the deregulation of the ratio between regulatory and conventional T cells becomes significant. Intravenous injection of Treg cells dampened parasite-specific CD8+ T cell immunity and affected parasite control in blood and tissues. Altogether, our results show that limited Treg cell response during the acute phase of T. cruzi infection enables the emergence of protective anti-parasite CD8+ T cell immunity and critically influences host resistance. |
| first_indexed | 2024-12-20T06:30:38Z |
| format | Article |
| id | doaj.art-89675fb7b2c64350af68960726eb620a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T06:30:38Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-89675fb7b2c64350af68960726eb620a2022-12-21T19:50:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02555412716Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell ImmunityCintia L. Araujo Furlan0Cintia L. Araujo Furlan1Jimena Tosello Boari2Jimena Tosello Boari3Constanza Rodriguez4Constanza Rodriguez5Fernando P. Canale6Fernando P. Canale7Facundo Fiocca Vernengo8Facundo Fiocca Vernengo9Santiago Boccardo10Santiago Boccardo11Cristian G. Beccaria12Cristian G. Beccaria13Véronique Adoue14Véronique Adoue15Véronique Adoue16Olivier Joffre17Olivier Joffre18Olivier Joffre19Adriana Gruppi20Adriana Gruppi21Carolina L. Montes22Carolina L. Montes23Eva V. Acosta Rodriguez24Eva V. Acosta Rodriguez25Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Córdoba, ArgentinaInstitut National de la Santé et de la Recherche Médicale, Toulouse, FranceCentre National de la Recherche Scientifique, Toulouse, FranceCentre de Physiopathologie de Toulouse Purpan, Université de Toulouse, Université Paul Sabatier, Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale, Toulouse, FranceCentre National de la Recherche Scientifique, Toulouse, FranceCentre de Physiopathologie de Toulouse Purpan, Université de Toulouse, Université Paul Sabatier, Toulouse, FranceDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Córdoba, ArgentinaWhile it is now acknowledged that CD4+ T cells expressing CD25 and Foxp3 (Treg cells) regulate immune responses and, consequently, influence the pathogenesis of infectious diseases, the regulatory response mediated by Treg cells upon infection by Trypanosoma cruzi was still poorly characterized. In order to understand the role of Treg cells during infection by this protozoan parasite, we determined in time and space the magnitude of the regulatory response and the phenotypic, functional and transcriptional features of the Treg cell population in infected mice. Contrary to the accumulation of Treg cells reported in most chronic infections in mice and humans, experimental T. cruzi infection was characterized by sustained numbers but decreased relative frequency of Treg cells. The reduction in Treg cell frequency resulted from a massive accumulation of effector immune cells, and inversely correlated with the magnitude of the effector immune response as well as with emergence of acute immunopathology. In order to understand the causes underlying the marked reduction in Treg cell frequency, we evaluated the dynamics of the Treg cell population and found a low proliferation rate and limited accrual of peripheral Treg cells during infection. We also observed that Treg cells became activated and acquired a phenotypic and transcriptional profile consistent with suppression of type 1 inflammatory responses. To assess the biological relevance of the relative reduction in Treg cells frequency observed during T. cruzi infection, we transferred in vitro differentiated Treg cells at early moments, when the deregulation of the ratio between regulatory and conventional T cells becomes significant. Intravenous injection of Treg cells dampened parasite-specific CD8+ T cell immunity and affected parasite control in blood and tissues. Altogether, our results show that limited Treg cell response during the acute phase of T. cruzi infection enables the emergence of protective anti-parasite CD8+ T cell immunity and critically influences host resistance.https://www.frontiersin.org/article/10.3389/fimmu.2018.02555/fullregulatory T (Treg) cellsTrypanosoma cruziimmunityCD8 cytotoxic T cells+pathogenesis |
| spellingShingle | Cintia L. Araujo Furlan Cintia L. Araujo Furlan Jimena Tosello Boari Jimena Tosello Boari Constanza Rodriguez Constanza Rodriguez Fernando P. Canale Fernando P. Canale Facundo Fiocca Vernengo Facundo Fiocca Vernengo Santiago Boccardo Santiago Boccardo Cristian G. Beccaria Cristian G. Beccaria Véronique Adoue Véronique Adoue Véronique Adoue Olivier Joffre Olivier Joffre Olivier Joffre Adriana Gruppi Adriana Gruppi Carolina L. Montes Carolina L. Montes Eva V. Acosta Rodriguez Eva V. Acosta Rodriguez Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell Immunity Frontiers in Immunology regulatory T (Treg) cells Trypanosoma cruzi immunity CD8 cytotoxic T cells+ pathogenesis |
| title | Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell Immunity |
| title_full | Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell Immunity |
| title_fullStr | Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell Immunity |
| title_full_unstemmed | Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell Immunity |
| title_short | Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell Immunity |
| title_sort | limited foxp3 regulatory t cells response during acute trypanosoma cruzi infection is required to allow the emergence of robust parasite specific cd8 t cell immunity |
| topic | regulatory T (Treg) cells Trypanosoma cruzi immunity CD8 cytotoxic T cells+ pathogenesis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02555/full |
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