Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi
Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the cli...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01548/full |
| _version_ | 1819264202273980416 |
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| author | Melisa Gorosito Serrán Jimena Tosello Boari Facundo Fiocca Vernengo Cristian G. Beccaría María C. Ramello Daniela A. Bermejo Amelia G. Cook Carola G. Vinuesa Carolina L. Montes Eva V. Acosta Rodriguez Adriana Gruppi |
| author_facet | Melisa Gorosito Serrán Jimena Tosello Boari Facundo Fiocca Vernengo Cristian G. Beccaría María C. Ramello Daniela A. Bermejo Amelia G. Cook Carola G. Vinuesa Carolina L. Montes Eva V. Acosta Rodriguez Adriana Gruppi |
| author_sort | Melisa Gorosito Serrán |
| collection | DOAJ |
| description | Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T. cruzi infection. Mice deficient in mature B cells (muMT mice) infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF-producing CD4+ T cells, and mortality. The increase in TNF-producing CD4+ T cells was accompanied by a reduction in IFNγ+CD4+ T cells and a decrease of the frequency of regulatory Foxp3+, IL-10+, and IL17+CD4+ T cells populations. The CD4+ T cell population activated by T. cruzi infection, in absence of mature B cells, had a high frequency of Ly6C+ cells and showed a lower expression of inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4+ T cells from infected muMT mice presented a high frequency of CD62LhiCD44− cells, which is commonly associated with a naïve phenotype. Through transfer experiments we demonstrated that CD4+ T cells from infected muMT mice were able to condition the CD4+ T cells response from infected wild-type mice. Interestingly, using Blimp-flox/flox-CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi-infected mice exhibited a higher number of TNF-producing CD4+ T cells. Our results showed that the absence of B cells during T. cruzi infection affected the T cell response at different levels and generated a favorable scenario for unconventional activation of CD4+ T cell leading to an uncontrolled effector response and inflammation. The product of B cell differentiation, the plasmablast/plasma cells, could be able to regulate TNF-producing CD4+ T cells since their absence favor the increase of the number of TNF+ CD4+ in T. cruzi-infected mice. |
| first_indexed | 2024-12-23T20:25:44Z |
| format | Article |
| id | doaj.art-b227416f13764d8c86e92c05631e1f2b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T20:25:44Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b227416f13764d8c86e92c05631e1f2b2022-12-21T17:32:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-11-01810.3389/fimmu.2017.01548289338Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruziMelisa Gorosito Serrán0Jimena Tosello Boari1Facundo Fiocca Vernengo2Cristian G. Beccaría3María C. Ramello4Daniela A. Bermejo5Amelia G. Cook6Carola G. Vinuesa7Carolina L. Montes8Eva V. Acosta Rodriguez9Adriana Gruppi10Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI – CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI – CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI – CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI – CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI – CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI – CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaDepartment of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, ACT, AustraliaDepartment of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, ACT, AustraliaCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI – CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI – CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI – CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaChagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T. cruzi infection. Mice deficient in mature B cells (muMT mice) infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF-producing CD4+ T cells, and mortality. The increase in TNF-producing CD4+ T cells was accompanied by a reduction in IFNγ+CD4+ T cells and a decrease of the frequency of regulatory Foxp3+, IL-10+, and IL17+CD4+ T cells populations. The CD4+ T cell population activated by T. cruzi infection, in absence of mature B cells, had a high frequency of Ly6C+ cells and showed a lower expression of inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4+ T cells from infected muMT mice presented a high frequency of CD62LhiCD44− cells, which is commonly associated with a naïve phenotype. Through transfer experiments we demonstrated that CD4+ T cells from infected muMT mice were able to condition the CD4+ T cells response from infected wild-type mice. Interestingly, using Blimp-flox/flox-CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi-infected mice exhibited a higher number of TNF-producing CD4+ T cells. Our results showed that the absence of B cells during T. cruzi infection affected the T cell response at different levels and generated a favorable scenario for unconventional activation of CD4+ T cell leading to an uncontrolled effector response and inflammation. The product of B cell differentiation, the plasmablast/plasma cells, could be able to regulate TNF-producing CD4+ T cells since their absence favor the increase of the number of TNF+ CD4+ in T. cruzi-infected mice.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01548/fullTrypanosoma cruziChagas diseaseB cellCD4+ T cellsinflammation |
| spellingShingle | Melisa Gorosito Serrán Jimena Tosello Boari Facundo Fiocca Vernengo Cristian G. Beccaría María C. Ramello Daniela A. Bermejo Amelia G. Cook Carola G. Vinuesa Carolina L. Montes Eva V. Acosta Rodriguez Adriana Gruppi Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi Frontiers in Immunology Trypanosoma cruzi Chagas disease B cell CD4+ T cells inflammation |
| title | Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi |
| title_full | Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi |
| title_fullStr | Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi |
| title_full_unstemmed | Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi |
| title_short | Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi |
| title_sort | unconventional pro inflammatory cd4 t cell response in b cell deficient mice infected with trypanosoma cruzi |
| topic | Trypanosoma cruzi Chagas disease B cell CD4+ T cells inflammation |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01548/full |
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