Trypanosoma cruzi Subverts Host Cell Sialylation and May Compromise Antigen-specific CD8(+) T Cell Responses

Trypanosoma cruzi Subverts Host Cell Sialylation and May Compromise Antigen-specific CD8(+) T Cell Responses

Author Freire-de-Lima, Leonardo Google Scholar
Alisson-Silva, Frederico Google Scholar
Carvalho, Sebastiao T. Google Scholar
Takiya, Christina M. Google Scholar
Rodrigues, Mauricio Martins Autor UNIFESP Google Scholar
DosReis, George A. Google Scholar
Mendonca-Previato, Lucia Google Scholar
Previato, Jose O. Google Scholar
Todeschini, Adriane R. Google Scholar
Institution Universidade Federal do Rio de Janeiro (UFRJ)
Universidade Federal de São Paulo (UNIFESP)
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.
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
National Institute for Science and Technology in Vaccines
Date 2010-04-30
Published in Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 285, n. 18, p. 13388-13396, 2010.
ISSN 0021-9258 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Biochemistry Molecular Biology Inc
Extent 13388-13396
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000276987700010

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