title: Trans-sialidase from Trypanosoma cruzi enhances the adhesion properties and fibronectin-driven migration of thymocytes.
abstract: In experimental Trypanosoma cruzi infections, severe thymic atrophy leads to release of activated CD4(+)CD8(+) double-positive (DP) T cells to the periphery. In humans, activated DP T cells are found in the blood in association with severe cardiac forms of human chronic Chagas disease. The mechanisms underlying the premature thymocyte release during the chagasic thymic atrophy remain elusive. We tested whether the migratory properties of intrathymic thymocytes are modulated by the parasite trans-sialidase (TS). We found that TS affected the dynamics of thymocytes undergoing intrathymic maturation, and these changes were accompanied by an increase in the number of recent DP thymic emigrants in the peripheral lymphoid organs. We demonstrated that increased percentages of blood DP T cell subsets were associated with augmented antibody titers against TS in chagasic patients with chronic cardiomyopathy. In vitro studies showed that TS was able to activate the MAPK pathway and actin filament mobilization in thymocytes. These effects were correlated with its ability to modulate the adhesion of thymocytes to thymic epithelial cells and their migration toward extracellular matrix. These findings point to effects of TS that could influence the escape of immature thymocytes in Chagas disease.
authors.affiliation: Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Ana Flávia F R
authors.initials: AF
authors.lastname: Nardy
authors.forename: João
authors.initials: J
authors.lastname: Luiz da Silva Filho
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Pérez
authors.forename: Juliana
authors.initials: J
authors.lastname: de Meis
authors.forename: Désio Aurélio
authors.initials: DA
authors.lastname: Farias-de-Oliveira
authors.forename: Luciana
authors.initials: L
authors.lastname: Penha
authors.forename: Isadora
authors.initials: I
authors.lastname: de Araújo Oliveira
authors.forename: Wagner B
authors.initials: WB
authors.lastname: Dias
authors.forename: Adriane R
authors.initials: AR
authors.lastname: Todeschini
authors.forename: Célio Geraldo
authors.initials: CG
authors.lastname: Freire-de-Lima
authors.forename: Maria
authors.initials: M
authors.lastname: Bellio
authors.forename: Celso
authors.initials: C
authors.lastname: Caruso-Neves
authors.forename: Ana Acácia
authors.initials: AA
authors.lastname: Pinheiro
authors.forename: Christina Maeda
authors.initials: CM
authors.lastname: Takiya
authors.forename: Oscar
authors.initials: O
authors.lastname: Bottasso
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.forename: Alexandre
authors.initials: A
authors.lastname: Morrot
mesh_terms: D000328:Adult; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D014355:Chagas Disease / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009439:Neuraminidase / Q000378:metabolism*; D060168:Thymocytes / Q000502:physiology*; D014349:Trypanosoma cruzi / Q000201:enzymology*
chemical_list: D005353:Fibronectins; D006023:Glycoproteins; C069715:trans-sialidase; D009439:Neuraminidase