Antibodies Inhibiting Trypanosoma cruzi Trans-Sialidase Activity In Sera From Human Infections

Leguizamón, María Susana; Campetella, Oscar; Russomando, Graciela; Almirón, María; Guillén, Ivalena; Cappa, S. M. González; Frasch, Alberto C.C.

doi:10.1093/infdis/170.6.1570

Cited by 40 publications

(48 citation statements)

References 13 publications

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“…These results are consistent with observations from others working with infected mice showing that thymus cellularity recovers after the parasitemia is controlled (18,19). By coincidence, TS-neutralizing Abs were detected in serum from 24 days pi (10).…”

Section: Discussionsupporting

confidence: 92%

“…cruzi trypomastigote-derived TS is glycosylphosphatidyl inositol-anchored on the parasite cell surface (8); it is shed to the milieu and detected in blood during the acute stage of Chagas' disease both in patients and in infected mice (9,10). Together with apoptosis induction in the immune system (7), other evidence supports that TS constitutes a virulence factor from T. cruzi (11)(12)(13).…”

mentioning

confidence: 99%

“…Together with apoptosis induction in the immune system (7), other evidence supports that TS constitutes a virulence factor from T. cruzi (11)(12)(13). Infection survivor animals and chronic Chagas' disease patients display neutralizing Abs that inhibit TS activity (14)(15)(16); therefore, the systemically distributed enzyme may only work early during the infectious process.…”

mentioning

confidence: 99%

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Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans -sialidase-induced apoptosis on nurse cells complex

Mucci

Hidalgo

Mocetti

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

101

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Trypanosoma cruzi, the causative agent of Chagas' disease, induces transient thymic aplasia early after infection-a phenomenon that stills lacks a molecular explanation. The parasite sheds an enzyme known as trans-sialidase (TS), which is able to direct transfer-sialyl residues among macromolecules. Because cell-surface sialylation is known to play a central role in the immune system, we tested whether the bloodstream-borne TS is responsible for the thymic alterations recorded during infection. We found that recombinant TS administered to naive mice was able to induce cell-count reduction mediated by apoptosis, mimicking cell subsets distribution and histologic findings observed during the acute phase of the infection. Thymocytes taken after TS treatment showed low response to Con A, although full ability to respond to IL-2 or IL-2 plus Con A was conserved, which resembles findings from infected animals. Alterations were found to revert several days after TS treatment. The administration of TS-neutralizing Abs to T. cruziinfected mice prevented thymus alterations. Results indicate that the primary target for the TS-induced apoptosis is the so-called ''nurse cell complex''. Therefore, we report here supporting evidence that TS is the virulence factor from T. cruzi responsible for the thymic alterations via apoptosis induction on the nurse cell complex, and that TS-neutralizing Abs elicitation during infection is associated with the reversion to thymic normal parameters.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans -sialidase-induced apoptosis on nurse cells complex

Mucci

Hidalgo

Mocetti

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

101

View full text Add to dashboard Cite

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“…Almost all individuals develop antibodies that recognize an epitope within the CTR of TS (3). Chagasic patients also generate antibodies specific for the Nterminal region of TS that strongly inhibit its enzymatic activity (19,20). Comparatively, chagasic antibodies preferentially recognize the native TS which contains the CTR rather than a recombinant TS which contains only the N-terminal catalytic domain (Figure 2).…”

Section: Immunogenic Properties Of Ts During Human Infection With T mentioning

confidence: 99%

Trans-sialidase delivered as a naked DNA vaccine elicits an immunological response similar to a Trypanosoma cruzi infection

Costa

Pereira-Chioccola

Ribeirão

et al. 1999

Braz J Med Biol Res

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Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, does not synthesize sialic acid, but expresses a trans-sialidase (TS) that catalyzes the transfer of sialic acid from host glycoconjugates to the parasite surface. Here, we review studies that characterize the immune response to the catalytic domain of the enzyme in humans during Chagas disease or in mice following immunization with the TS gene. In both cases, there are antibodies that strongly inhibit the enzymatic activity and generation of interferon-g-producing T cells.

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“…Almost all individuals develop antibodies that recognize an epitope composed of amino acid repetitions located at the carboxy-terminal region of TS (19). Chagasic patients also generate antibodies specific for the Nterminal region of TS that strongly inhibit its enzymatic activity (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

The non-palindromic adaptor-PCR method for the identification of the T-cell receptor genes of an interferon-gamma-secreting T-cell hybridomaspecific for trans-sialidase, an immunodominant Trypanosoma cruzi antigen

Hiyane

Boscardin

Rodrigues

2006

Braz J Med Biol Res

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Cloning of the T-cell receptor genes is a critical step when generating T-cell receptor transgenic mice. Because T-cell receptor molecules are clonotypical, isolation of their genes requires reverse transcriptaseassisted PCR using primers specific for each different Vα or Vß genes or by the screening of cDNA libraries generated from RNA obtained from each individual T-cell clone. Although feasible, these approaches are laborious and costly. The aim of the present study was to test the application of the non-palindromic adaptor-PCR method as an alternative to isolate the genes encoding the T-cell receptor of an antigenspecific T-cell hybridoma. For this purpose, we established hybridomas specific for trans-sialidase, an immunodominant Trypanosoma cruzi antigen. These T-cell hybridomas were characterized with regard to their ability to secrete interferon-γ, IL-4, and IL-10 after stimulation with the antigen. A CD3 + , CD4 + , CD8 -interferon-γ-producing hybridoma was selected for the identification of the variable regions of the T-cell receptor by the non-palindromic adaptor-PCR method. Using this methodology, we were able to rapidly and efficiently determine the variable regions of both T-cell receptor chains. The results obtained by the non-palindromic adaptor-PCR method were confirmed by the isolation and sequencing of the complete cDNA genes and by the recognition with a specific antibody against the T-cell receptor variable ß chain. We conclude that the nonpalindromic adaptor-PCR method can be a valuable tool for the identification of the T-cell receptor transcripts of T-cell hybridomas and may facilitate the generation of T-cell receptor transgenic mice.

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Antibodies Inhibiting Trypanosoma cruzi Trans-Sialidase Activity In Sera From Human Infections

Cited by 40 publications

References 13 publications

Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans -sialidase-induced apoptosis on nurse cells complex

Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans -sialidase-induced apoptosis on nurse cells complex

Trans-sialidase delivered as a naked DNA vaccine elicits an immunological response similar to a Trypanosoma cruzi infection

The non-palindromic adaptor-PCR method for the identification of the T-cell receptor genes of an interferon-gamma-secreting T-cell hybridomaspecific for trans-sialidase, an immunodominant Trypanosoma cruzi antigen

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