TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells

Previous studies revealed a significant production of inflammatory cytokines together with severe thymic atrophy and thymocyte migratory disturbances during experimental Chagas disease. Migratory activity of thymocytes and mature T cells seem to be finely tuned by cytokines, chemokines and extracell...

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Autores principales: Pérez, Ana Rosa, Berbert, Luiz Ricardo, Lepletier, Ailin, Revelli, Silvia, Bottasso, Oscar, Silva-Barbosa, Suse Dayse, Savino, Wilson
Formato: artículo article publishedVersion
Lenguaje:Inglés
Publicado: PLOS (Public Library of Science) 2014
Materias:
Trypanosoma cruzi
Atrophy
Cell migration
Lymphoid organs
Spleen
Thymocytes
Thymus
Acceso en línea:http://hdl.handle.net/2133/3079
http://hdl.handle.net/2133/3079
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-3079
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv en
topic Trypanosoma cruzi
Atrophy
Cell migration
Lymphoid organs
Spleen
Thymocytes
Thymus
spellingShingle Trypanosoma cruzi
Atrophy
Cell migration
Lymphoid organs
Spleen
Thymocytes
Thymus
Pérez, Ana Rosa
Berbert, Luiz Ricardo
Lepletier, Ailin
Revelli, Silvia
Bottasso, Oscar
Silva-Barbosa, Suse Dayse
Savino, Wilson
TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells
topic_facet Trypanosoma cruzi
Atrophy
Cell migration
Lymphoid organs
Spleen
Thymocytes
Thymus
description Previous studies revealed a significant production of inflammatory cytokines together with severe thymic atrophy and thymocyte migratory disturbances during experimental Chagas disease. Migratory activity of thymocytes and mature T cells seem to be finely tuned by cytokines, chemokines and extracellular matrix (ECM) components. Systemic TNF-α is enhanced during infection and appears to be crucial in the response against the parasite. However, it also seems to be involved in disease pathology, since it is implicated in the arrival of T cells to effector sites, including the myocardium. Herein, we analyzed the role of TNF-α in the migratory activity of thymocytes in Trypanosoma cruzi (T. cruzi) acutely-infected mice. We found increased expression and deposition of TNF-α in the thymus of infected animals compared to controls, accompanied by increased co-localization of fibronectin, a cell migration-related ECM molecule, whose contents in the thymus of infected mice is also augmented. In-vivo studies showed an enhanced export of thymocytes in T. cruzi-infected mice, as ascertained by intrathymic injection of FITC alone or in combination with TNF-α. The increase of immature CD4+CD8+ T cells in secondary lymphoid organs was even more clear-cut when TNF-α was co-injected with FITC. Ex-vivo transmigration assays also revealed higher number of migrating cells when TNF-α was added onto fibronectin lattices, with higher input of all thymocyte subsets, including immature CD4+CD8+. Infected animals also exhibit enhanced levels of expression of both mRNA TNF-α receptors in the CD4+CD8+ subpopulation. Our findings suggest that in T. cruzi acute infection, when TNF-α is complexed with fibronectin, it favours the altered migration of thymocytes, promoting the release of mature and immature T cells to different compartments of the immune system. Conceptually, this work reinforces the notion that thymocyte migration is a multivectorial biological event in health and disease, and that TNF-α is a further player in the process.
format artículo
article
publishedVersion
author Pérez, Ana Rosa
Berbert, Luiz Ricardo
Lepletier, Ailin
Revelli, Silvia
Bottasso, Oscar
Silva-Barbosa, Suse Dayse
Savino, Wilson
author_facet Pérez, Ana Rosa
Berbert, Luiz Ricardo
Lepletier, Ailin
Revelli, Silvia
Bottasso, Oscar
Silva-Barbosa, Suse Dayse
Savino, Wilson
author_sort Pérez, Ana Rosa
title TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells
title_short TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells
title_full TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells
title_fullStr TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells
title_full_unstemmed TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells
title_sort tnf-α is involved in the abnormal thymocyte migration during experimental trypanosoma cruzi infection and favors the export of immature cells
publisher PLOS (Public Library of Science)
publishDate 2014
url http://hdl.handle.net/2133/3079
http://hdl.handle.net/2133/3079
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