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

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dc.contributor.author Pérez, Ana Rosa
dc.contributor.author Berbert, Luiz Ricardo
dc.contributor.author Lepletier, Ailin
dc.contributor.author Revelli, Silvia
dc.contributor.author Bottasso, Oscar
dc.contributor.author Silva-Barbosa, Suse Dayse
dc.contributor.author Savino, Wilson
dc.date.accessioned 2014-03-26T18:42:10Z
dc.date.available 2014-03-26T18:42:10Z
dc.date.issued 2012-03-26
dc.identifier.citation Pe´rez AR, Berbert LR, Lepletier A, Revelli S, Bottasso O, et al. (2012) TNF-a Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells. PLoS ONE 7(3): e34360. doi:10.1371/journal.pone.0034360 es
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/2133/3079
dc.description.abstract 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. es
dc.format application/pdf
dc.language.iso en es
dc.publisher PLOS (Public Library of Science) es
dc.rights openAccess
dc.subject Trypanosoma cruzi es
dc.subject Atrophy es
dc.subject Cell migration es
dc.subject Lymphoid organs es
dc.subject Spleen es
dc.subject Thymocytes es
dc.subject Thymus es
dc.title TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells es
dc.type artículo
dc.type article
dc.type publishedVersion
dc.description.peerreviewed Peer reviewed es
dc.relation.publisherversion 10.1371/journal.pone.0034360 es
dc.rights.text © 2012 Pérez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. es
dc.description.affiliation Fil: Pérez, Ana Rosa. Universidad Nacional de Rosario, Facultad de Ciencias Médicas, Instituto de Inmunología; Argentina.
dc.description.affiliation Fil: Revelli, Silvia. Universidad Nacional de Rosario, Facultad de Ciencias Médicas, Instituto de Inmunología; Argentina.
dc.description.affiliation Fil: Berbert, Luiz Ricardo. Instituto Oswaldo Cruz, Rio de Janeiro; Brasil
dc.description.affiliation Fil: Lepletier, Ailin. Instituto Oswaldo Cruz, Rio de Janeiro; Brasil
dc.description.affiliation Fil: Bottasso, Oscar. Universidad Nacional de Rosario, Facultad de Ciencias Médicas, Instituto de Inmunología; Argentina.


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