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dc.contributor.author
Ruiz Díaz, Pablo Daniel
dc.contributor.author
Mucci, Juan Sebastián
dc.contributor.author
Meira, María Ana
dc.contributor.author
Bogliotti, Yanina
dc.contributor.author
Musikant, Alejandro Daniel
dc.contributor.author
Leguizamon, Maria Susana
dc.contributor.author
Campetella, Oscar Eduardo
dc.date.available
2018-07-03T14:16:50Z
dc.date.issued
2015-05
dc.identifier.citation
Ruiz Díaz, Pablo Daniel; Mucci, Juan Sebastián; Meira, María Ana; Bogliotti, Yanina; Musikant, Alejandro Daniel; et al.; Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells; American Society for Microbiology; Infection and Immunity; 83; 5; 5-2015; 2099-2108
dc.identifier.issn
0019-9567
dc.identifier.uri
http://hdl.handle.net/11336/50994
dc.description.abstract
The trans-sialidases (TSs) from Trypanosoma cruzi, the agent of Chagas disease, are virulence factors shed to the bloodstream that induce strong alterations in the immune system. Here, we report that both enzymatically active TS (aTS) and its lectinlike isoform (iTS) disturb CD4 T cell physiology, inducing downregulation of Th1 cell functionality and in vivo cell expansion. By using ovalbumin-specific DO11.10 cells as tracers of clones developing the Th1 phenotype, we found that the infection induced significant amounts of gamma interferon (IFN-γ) but low levels of interleukin 2 (IL-2) and increased IL-4 production in vivo, in agreement with a mixed T helper response. The production of cytokines associated with the Th2 phenotype was prevented by passive transfer of anti-TS neutralizing antibodies. TSs also reduced the T cell receptor signaling as assayed by Zap-70 phosphorylation. TSs also reduced IL-2 and IFN-γ secretion, with a concomitant increase in IL-4 production and then an unbalancing of the CD4 T cell response toward the Th2 phenotype. This effect was prevented by using anti-IL-10 neutralizing antibodies or IL-10-/- antigen-presenting cells, supporting the subversion of this regulatory pathway. In support, TSs stimulated IL-10 secretion by antigen-presenting cells during their interaction with CD4 T cells. When polarized cells were stimulated in the presence of TSs, the secretion of IL-2 and IFN-γ was strongly downregulated in Th1 cells, while IL-2 production was upregulated in Th2 cells. Although the Th1 response is associated with host survival, it may simultaneously induce extensive damage to infected tissues. Thus, by delaying the elicitation of the Th1 response and limiting its effector properties, TSs restrain the cell response, supporting T. cruzi colonization and persistence while favoring host survival.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society for Microbiology
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Trypanosoma Cruzi
dc.subject
Trans-Sialidase
dc.subject
Cd4 T Cells
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Th1/Th2
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Parasitología
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-19T16:54:10Z
dc.journal.volume
83
dc.journal.number
5
dc.journal.pagination
2099-2108
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Ruiz Díaz, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
dc.description.fil
Fil: Mucci, Juan Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
dc.description.fil
Fil: Meira, María Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
dc.description.fil
Fil: Bogliotti, Yanina. Universidad Nacional de San Martín; Argentina
dc.description.fil
Fil: Musikant, Alejandro Daniel. Universidad de Buenos Aires. Facultad de Medicina; Argentina
dc.description.fil
Fil: Leguizamon, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
dc.description.fil
Fil: Campetella, Oscar Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
dc.journal.title
Infection and Immunity
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1128/IAI.00031-15
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://iai.asm.org/content/83/5/2099
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