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

dc.contributor.authorPérez, Ana Rosa
dc.contributor.authorBerbert, Luiz Ricardo
dc.contributor.authorLepletier, Ailin
dc.contributor.authorRevelli, Silvia
dc.contributor.authorBottasso, Oscar
dc.contributor.authorSilva-Barbosa, Suse Dayse
dc.contributor.authorSavino, Wilson
dc.date.accessioned2014-03-26T18:42:10Z
dc.date.available2014-03-26T18:42:10Z
dc.date.issued2012-03-26
dc.description.abstractPrevious 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.description.affiliationFil: Pérez, Ana Rosa. Universidad Nacional de Rosario, Facultad de Ciencias Médicas, Instituto de Inmunología; Argentina.
dc.description.affiliationFil: Revelli, Silvia. Universidad Nacional de Rosario, Facultad de Ciencias Médicas, Instituto de Inmunología; Argentina.
dc.description.affiliationFil: Berbert, Luiz Ricardo. Instituto Oswaldo Cruz, Rio de Janeiro; Brasil
dc.description.affiliationFil: Lepletier, Ailin. Instituto Oswaldo Cruz, Rio de Janeiro; Brasil
dc.description.affiliationFil: Bottasso, Oscar. Universidad Nacional de Rosario, Facultad de Ciencias Médicas, Instituto de Inmunología; Argentina.
dc.description.peerreviewedPeer reviewedes
dc.formatapplication/pdf
dc.identifier.citationPe´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.0034360es
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/2133/3079
dc.language.isoenes
dc.publisherPLOS (Public Library of Science)es
dc.relation.publisherversion10.1371/journal.pone.0034360es
dc.rightsopenAccess
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.subjectTrypanosoma cruzies
dc.subjectAtrophyes
dc.subjectCell migrationes
dc.subjectLymphoid organses
dc.subjectSpleenes
dc.subjectThymocyteses
dc.subjectThymuses
dc.titleTNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cellses
dc.typeartículo
dc.typearticle
dc.typepublishedVersion

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