IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection
The IL-17 family contributes to host defense against many intracellular pathogens by mechanisms that are not fully understood. CD8+ T lymphocytes are key elements against intracellular microbes, and their survival and ability to mount cytotoxic responses are orchestrated by several cytokines. Here,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02347/full |
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| author | Jimena Tosello Boari Jimena Tosello Boari Cintia L. Araujo Furlan Cintia L. Araujo Furlan Facundo Fiocca Vernengo Facundo Fiocca Vernengo Constanza Rodriguez Constanza Rodriguez María C. Ramello María C. Ramello María C. Amezcua Vesely María C. Amezcua Vesely Melisa Gorosito Serrán Melisa Gorosito Serrán Nicolás G. Nuñez Nicolás G. Nuñez Wilfrid Richer Wilfrid Richer Eliane Piaggio Eliane Piaggio Carolina L. Montes Carolina L. Montes Adriana Gruppi Adriana Gruppi Eva V. Acosta Rodríguez Eva V. Acosta Rodríguez |
| author_facet | Jimena Tosello Boari Jimena Tosello Boari Cintia L. Araujo Furlan Cintia L. Araujo Furlan Facundo Fiocca Vernengo Facundo Fiocca Vernengo Constanza Rodriguez Constanza Rodriguez María C. Ramello María C. Ramello María C. Amezcua Vesely María C. Amezcua Vesely Melisa Gorosito Serrán Melisa Gorosito Serrán Nicolás G. Nuñez Nicolás G. Nuñez Wilfrid Richer Wilfrid Richer Eliane Piaggio Eliane Piaggio Carolina L. Montes Carolina L. Montes Adriana Gruppi Adriana Gruppi Eva V. Acosta Rodríguez Eva V. Acosta Rodríguez |
| author_sort | Jimena Tosello Boari |
| collection | DOAJ |
| description | The IL-17 family contributes to host defense against many intracellular pathogens by mechanisms that are not fully understood. CD8+ T lymphocytes are key elements against intracellular microbes, and their survival and ability to mount cytotoxic responses are orchestrated by several cytokines. Here, we demonstrated that IL-17RA-signaling cytokines sustain pathogen-specific CD8+ T cell immunity. The absence of IL-17RA and IL-17A/F during Trypanosoma cruzi infection resulted in increased tissue parasitism and reduced frequency of parasite-specific CD8+ T cells. Impaired IL-17RA-signaling in vivo increased apoptosis of parasite-specific CD8+ T cells, while in vitro recombinant IL-17 down-regulated the pro-apoptotic protein BAD and promoted the survival of activated CD8+ T cells. Phenotypic, functional, and transcriptomic profiling showed that T. cruzi-specific CD8+ T cells derived from IL-17RA-deficient mice presented features of cell dysfunction. PD-L1 blockade partially restored the magnitude of CD8+ T cell responses and parasite control in these mice. Adoptive transfer experiments established that IL-17RA-signaling is intrinsically required for the proper maintenance of functional effector CD8+ T cells. Altogether, our results identify IL-17RA and IL-17A as critical factors for sustaining CD8+ T cell immunity to T. cruzi. |
| first_indexed | 2024-12-21T15:13:56Z |
| format | Article |
| id | doaj.art-079d5f04e628454aa28f96a60e4aaed2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T15:13:56Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-079d5f04e628454aa28f96a60e4aaed22022-12-21T18:59:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02347403363IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi InfectionJimena Tosello Boari0Jimena Tosello Boari1Cintia L. Araujo Furlan2Cintia L. Araujo Furlan3Facundo Fiocca Vernengo4Facundo Fiocca Vernengo5Constanza Rodriguez6Constanza Rodriguez7María C. Ramello8María C. Ramello9María C. Amezcua Vesely10María C. Amezcua Vesely11Melisa Gorosito Serrán12Melisa Gorosito Serrán13Nicolás G. Nuñez14Nicolás G. Nuñez15Wilfrid Richer16Wilfrid Richer17Eliane Piaggio18Eliane Piaggio19Carolina L. Montes20Carolina L. Montes21Adriana Gruppi22Adriana Gruppi23Eva V. Acosta Rodríguez24Eva V. Acosta Rodríguez25Departamento 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, ArgentinaSiRIC TransImm “Translational Immunotherapy Team,” Translational Research Department, Research Center, PSL Research University, INSERM U932, Institut Curie, Paris, FranceCentre d'Investigation Clinique Biothérapie CICBT 1428, Institut Curie, Paris, FranceSiRIC TransImm “Translational Immunotherapy Team,” Translational Research Department, Research Center, PSL Research University, INSERM U932, Institut Curie, Paris, FranceCentre d'Investigation Clinique Biothérapie CICBT 1428, Institut Curie, Paris, FranceSiRIC TransImm “Translational Immunotherapy Team,” Translational Research Department, Research Center, PSL Research University, INSERM U932, Institut Curie, Paris, FranceCentre d'Investigation Clinique Biothérapie CICBT 1428, Institut Curie, Paris, 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, ArgentinaThe IL-17 family contributes to host defense against many intracellular pathogens by mechanisms that are not fully understood. CD8+ T lymphocytes are key elements against intracellular microbes, and their survival and ability to mount cytotoxic responses are orchestrated by several cytokines. Here, we demonstrated that IL-17RA-signaling cytokines sustain pathogen-specific CD8+ T cell immunity. The absence of IL-17RA and IL-17A/F during Trypanosoma cruzi infection resulted in increased tissue parasitism and reduced frequency of parasite-specific CD8+ T cells. Impaired IL-17RA-signaling in vivo increased apoptosis of parasite-specific CD8+ T cells, while in vitro recombinant IL-17 down-regulated the pro-apoptotic protein BAD and promoted the survival of activated CD8+ T cells. Phenotypic, functional, and transcriptomic profiling showed that T. cruzi-specific CD8+ T cells derived from IL-17RA-deficient mice presented features of cell dysfunction. PD-L1 blockade partially restored the magnitude of CD8+ T cell responses and parasite control in these mice. Adoptive transfer experiments established that IL-17RA-signaling is intrinsically required for the proper maintenance of functional effector CD8+ T cells. Altogether, our results identify IL-17RA and IL-17A as critical factors for sustaining CD8+ T cell immunity to T. cruzi.https://www.frontiersin.org/article/10.3389/fimmu.2018.02347/fullIL-17chagas diseaseimmunitycellularCD8+ T cellsexhausted T cells |
| spellingShingle | Jimena Tosello Boari Jimena Tosello Boari Cintia L. Araujo Furlan Cintia L. Araujo Furlan Facundo Fiocca Vernengo Facundo Fiocca Vernengo Constanza Rodriguez Constanza Rodriguez María C. Ramello María C. Ramello María C. Amezcua Vesely María C. Amezcua Vesely Melisa Gorosito Serrán Melisa Gorosito Serrán Nicolás G. Nuñez Nicolás G. Nuñez Wilfrid Richer Wilfrid Richer Eliane Piaggio Eliane Piaggio Carolina L. Montes Carolina L. Montes Adriana Gruppi Adriana Gruppi Eva V. Acosta Rodríguez Eva V. Acosta Rodríguez IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection Frontiers in Immunology IL-17 chagas disease immunity cellular CD8+ T cells exhausted T cells |
| title | IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection |
| title_full | IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection |
| title_fullStr | IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection |
| title_full_unstemmed | IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection |
| title_short | IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection |
| title_sort | il 17ra signaling modulates cd8 t cell survival and exhaustion during trypanosoma cruzi infection |
| topic | IL-17 chagas disease immunity cellular CD8+ T cells exhausted T cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02347/full |
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