title: Trypanosoma cruzi subverts host cell sialylation and may compromise antigen-specific CD8+ T cell responses.
abstract: Upon activation, cytotoxic CD8(+) T lymphocytes are desialylated exposing beta-galactose residues in a physiological change that enhances their effector activity and that can be monitored on the basis of increased binding of the lectin peanut agglutinin. Herein, we investigated the impact of sialylation mediated by trans-sialidase, a specific and unique Trypanosoma transglycosylase for sialic acid, on CD8(+) T cell response of mice infected with T. cruzi. Our data demonstrate that T. cruzi uses its trans-sialidase enzyme to resialylate the CD8(+) T cell surface, thereby dampening antigen-specific CD8(+) T cell response that might favor its own persistence in the mammalian host. Binding of the monoclonal antibody S7, which recognizes sialic acid-containing epitopes on the 115-kDa isoform of CD43, was augmented on CD8(+) T cells from ST3Gal-I-deficient infected mice, indicating that CD43 is one sialic acid acceptor for trans-sialidase activity on the CD8(+) T cell surface. The cytotoxic activity of antigen-experienced CD8(+) T cells against the immunodominant trans-sialidase synthetic peptide IYNVGQVSI was decreased following active trans-sialidase-mediated resialylation in vitro and in vivo. Inhibition of the parasite's native trans-sialidase activity during infection strongly decreased CD8(+) T cell sialylation, reverting it to the glycosylation status expected in the absence of parasite manipulation increasing mouse survival. Taken together, these results demonstrate, for the first time, that T. cruzi subverts sialylation to attenuate CD8(+) T cell interactions with peptide-major histocompatibility complex class I complexes. CD8(+) T cell resialylation may represent a sophisticated strategy to ensure lifetime host parasitism.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Ilha do Fundão, 21949-900 Rio de Janeiro, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Freire-de-Lima
authors.forename: Frederico
authors.initials: F
authors.lastname: Alisson-Silva
authors.forename: Sebastião T
authors.initials: ST
authors.lastname: Carvalho
authors.forename: Christina M
authors.initials: CM
authors.lastname: Takiya
authors.forename: Maurício M
authors.initials: MM
authors.lastname: Rodrigues
authors.forename: George A
authors.initials: GA
authors.lastname: DosReis
authors.forename: Lucia
authors.initials: L
authors.lastname: Mendonça-Previato
authors.forename: José O
authors.initials: JO
authors.lastname: Previato
authors.forename: Adriane R
authors.initials: AR
authors.lastname: Todeschini
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014355:Chagas Disease / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006031:Glycosylation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051917:Leukosialin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019158:N-Acetylneuraminic Acid / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009439:Neuraminidase / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012799:Sialyltransferases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D051917:Leukosialin; D010455:Peptides; D015800:Protozoan Proteins; C497863:Spn protein, mouse; D012799:Sialyltransferases; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase