Navegar

Colección

Datos Estadísticas

Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

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. © 2015, American Society for Microbiology.

Registro:

Documento: Artículo
Título:Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells
Autor:Díaz, P.R.; Mucci, J.; Meira, M.A.; Bogliotti, Y.; Musikant, D.; Leguizamón, M.S.; Campetella, O.
Filiación:Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, San Martín, Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
Instituto de Microbiología y Parasitología Médica, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Department of Animal Science, University of California, Davis, CA, United States
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:gamma interferon; interleukin 10; interleukin 2; interleukin 4; neutralizing antibody; ovalbumin; protein kinase ZAP 70; sialidase; T lymphocyte receptor; trans sialidase; unclassified drug; gamma interferon; glycoprotein; immunologic factor; interleukin 10; interleukin 2; interleukin 4; sialidase; trans-sialidase; virulence factor; animal cell; animal experiment; antigen presenting cell; Article; CD4+ T lymphocyte; cell expansion; cell interaction; cell stimulation; cell survival; clone; controlled study; cytokine production; cytokine release; down regulation; effector cell; enzyme activity; in vivo study; male; mouse; nonhuman; parasite survival; phenotype; polarization; priority journal; protein expression; Th1 cell; Trypanosoma cruzi; upregulation; animal; Bagg albino mouse; immune evasion; immunology; metabolism; secretion (process); Th1 cell; Trypanosoma cruzi; Animals; Glycoproteins; Immune Evasion; Immunologic Factors; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-4; Male; Mice, Inbred BALB C; Neuraminidase; Th1 Cells; Trypanosoma cruzi; Virulence Factors
Año:2015
Volumen:83
Número:5
Página de inicio:2099
Página de fin:2108
DOI: http://dx.doi.org/10.1128/IAI.00031-15
Título revista:Infection and Immunity
Título revista abreviado:Infect. Immun.
ISSN:00199567
CODEN:INFIB
CAS:gamma interferon, 82115-62-6; interleukin 2, 85898-30-2; ovalbumin, 77466-29-6; protein kinase ZAP 70, 148047-34-1; sialidase, 9001-67-6; Glycoproteins; Immunologic Factors; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-4; Neuraminidase; trans-sialidase; Virulence Factors
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00199567_v83_n5_p2099_Diaz

Referencias:

  • Rassi Jr, A., Rassi, A., Marin-Neto, J.A., Chagas disease (2010) Lancet, 375, pp. 1388-1402. , http://dx.doi.org/10.1016/S0140-6736(10)60061-X
  • Reed, S.G., Larson, C.L., Speer, C.A., Suppression of cell-mediated immunity in experimental Chagas' disease (1977) Z Parasitenkd, 52, pp. 11-17. , http://dx.doi.org/10.1007/BF00380553
  • Rowland, E.C., Kuhn, R.E., Suppression of cellular responses in mice during Trypanosoma cruzi infections (1978) Infect Immun, 20, pp. 393-397
  • Tarleton, R.L., Scott, D.W., Initial induction of immunity, followed by suppression of responses to parasite antigens during Trypanosoma cruzi infection of mice (1987) Parasite Immunol, 9, pp. 579-589. , http://dx.doi.org/10.1111/j.1365-3024.1987.tb00531.x
  • de Meis, J., Morrot, A., Farias-de-Oliveira, D.A., Villa-Verde, D.M., Savino, W., Differential regional immune response in Chagas disease (2009) PLoS Negl Trop Dis, 3. , http://dx.doi.org/10.1371/journal.pntd.0000417
  • Kierszenbaum, F., Sztein, M.B., Mechanisms underlying immunosuppression induced by Trypanosoma cruzi (1990) Parasitol Today, 6, pp. 261-264. , http://dx.doi.org/10.1016/0169-4758(90)90187-9
  • Nunes, M.P., Andrade, R.M., Lopes, M.F., DosReis, G.A., Activationinduced T cell death exacerbates Trypanosoma cruzi replication in macrophages cocultured with CD4+ T lymphocytes from infected hosts (1998) J Immunol, 160, pp. 1313-1319
  • Zúñiga, E., Motran, C.C., Montes, C.L., Yagita, H., Gruppi, A., Trypanosoma cruzi infection selectively renders parasite-specific IgG+ B lymphocytes susceptible to Fas/Fas ligand-mediated fratricide (2002) J Immunol, 168, pp. 3965-3973. , http://dx.doi.org/10.4049/jimmunol.168.8.3965
  • Van Overtvelt, L., Andrieu, M., Verhasselt, V., Connan, F., Choppin, J., Vercruysse, V., Goldman, M., Vray, B., Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8(+) T lymphocytes (2002) Int Immunol, 14, pp. 1135-1144. , http://dx.doi.org/10.1093/intimm/dxf077
  • Tarleton, R.L., Grusby, M.J., Zhang, L., Increased susceptibility of Stat4-deficient and enhanced resistance in Stat6-deficient mice to infection with Trypanosoma cruzi (2000) J Immunol, 165, pp. 1520-1525. , http://dx.doi.org/10.4049/jimmunol.165.3.1520
  • Kumar, S., Tarleton, R.L., Antigen-specific Th1 but not Th2 cells provide protection from lethal Trypanosoma cruzi infection in mice (2001) J Immunol, 166, pp. 4596-4603. , http://dx.doi.org/10.4049/jimmunol.166.7.4596
  • Albareda, M.C., Laucella, S.A., Alvarez, M.G., Armenti, A.H., Bertochi, G., Tarleton, R.L., Postan, M., Trypanosoma cruzi modulates the profile of memory CD8+ T cells in chronic Chagas' disease patients (2006) Int Immunol, 18, pp. 465-471. , http://dx.doi.org/10.1093/intimm/dxh387
  • Barbosa de Oliveira, L.C., Curotto de Lafaille, M.A., Collet de Araujo Lima, G.M., de Almeida Abrahamsohn, I., Antigen-specific IL-4- and IL-10-secreting CD4+ lymphocytes increase in vivo susceptibility to Trypanosoma cruzi infection (1996) Cell Immunol, 170, pp. 41-53. , http://dx.doi.org/10.1006/cimm.1996.0132
  • Mucci, J., Risso, M.G., Leguizamón, M.S., Frasch, A.C., Campetella, O., The trans-sialidase from Trypanosoma cruzi triggers apoptosis by target cell sialylation (2006) Cell Microbiol, 8, pp. 1086-1095. , http://dx.doi.org/10.1111/j.1462-5822.2006.00689.x
  • Muiá, R.P., Yu, H., Prescher, J.A., Hellman, U., Chen, X., Bertozzi, C.R., Campetella, O., Identification of glycoproteins targeted by Trypanosoma cruzi trans-sialidase, a virulence factor that disturbs lymphocyte glycosylation (2010) Glycobiology, 20, pp. 833-842. , http://dx.doi.org/10.1093/glycob/cwq037
  • Leguizamón, M.S., Mocetti, E., Garcia Rivello, H., Argibay, P., Campetella, O., trans-sialidase from Trypanosoma cruzi induces apoptosis in cells from the immune system in vivo (1999) J Infect Dis, 180, pp. 1398-1402. , http://dx.doi.org/10.1086/315001
  • Risso, M.G., Pitcovsky, T.A., Caccuri, R.L., Campetella, O., Leguizamón, M.S., Immune system pathogenesis is prevented by the neutralization of the systemic trans-sialidase from Trypanosoma cruzi during severe infections (2007) Parasitology, 134, pp. 503-510. , http://dx.doi.org/10.1017/S0031182006001752
  • Tribulatti, M.V., Mucci, J., Van Rooijen, N., Leguizamón, M.S., Campetella, O., The trans-sialidase from Trypanosoma cruzi induces thrombocytopenia during acute Chagas' disease by reducing the platelet sialic acid contents (2005) Infect Immun, 73, pp. 201-207. , http://dx.doi.org/10.1128/IAI.73.1.201-207.2005
  • de Titto, E.H., Araujo, F.G., Serum neuraminidase activity and hematological alterations in acute human Chagas' disease (1988) Clin Immunol Immunopathol, 46, pp. 157-161. , http://dx.doi.org/10.1016/0090-1229(88)90016-5
  • Mucci, J., Hidalgo, A., Mocetti, E., Argibay, P.F., Leguizamón, M.S., Campetella, O., Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans-sialidase-induced apoptosis on nurse cells complex (2002) Proc Natl Acad Sci U S A, 99, pp. 3896-3901. , http://dx.doi.org/10.1073/pnas.052496399
  • Vercelli, C.A., Hidalgo, A.M., Hyon, S.H., Argibay, P.F., Trypanosoma cruzi trans-sialidase inhibits human lymphocyte proliferation by nonapoptotic mechanisms: implications in pathogenesis and transplant immunology (2005) Transplant Proc, 37, pp. 4594-4597. , http://dx.doi.org/10.1016/j.transproceed.2005.10.013
  • Risso, M.G., Garbarino, G.B., Mocetti, E., Campetella, O., González Cappa, S.M., Buscaglia, C.A., Leguizamón, M.S., Differential expression of a virulence factor, the trans-sialidase, by the main Trypanosoma cruzi phylogenetic lineages (2004) J Infect Dis, 189, pp. 2250-2259. , http://dx.doi.org/10.1086/420831
  • Freire-de-Lima, L., Alisson-Silva, F., Carvalho, S.T., Takiya, C.M., Rodrigues, M.M., Dosreis, G.A., Mendonca-Previato, L., Todeschini, A.R., Trypanosoma cruzi subverts host cell sialylation and may compromise antigen-specific CD8+ T cell responses (2010) J Biol Chem, 285, pp. 13386-13396. , http://dx.doi.org/10.1074/jbc.M109.096305
  • Cremona, M.L., Sanchez, D.O., Frasch, A.C., Campetella, O., A single tyrosine differentiates active and inactive Trypanosoma cruzi transsialidases (1995) Gene, 160, pp. 123-128. , http://dx.doi.org/10.1016/0378-1119(95)00175-6
  • Cremona, M.L., Campetella, O., Sanchez, D.O., Frasch, A.C., Enzymically inactive members of the trans-sialidase family from Trypanosoma cruzi display beta-galactose binding activity (1999) Glycobiology, 9, pp. 581-587. , http://dx.doi.org/10.1093/glycob/9.6.581
  • Todeschini, A.R., Girard, M.F., Wieruszeski, J.M., Nunes, M.P., DosReis, G.A., Mendonca-Previato, L., Previato, J.O., trans-sialidase from Trypanosoma cruzi binds host T-lymphocytes in a lectin manner (2002) J Biol Chem, 277, pp. 45962-45968. , http://dx.doi.org/10.1074/jbc.M203185200
  • Guide for the care and use of laboratory animals (2011), 8th ed. National Academies Press, Washington, DC; Kearney, E.R., Pape, K.A., Loh, D.Y., Jenkins, M.K., Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo (1994) Immunity, 1, pp. 327-339. , http://dx.doi.org/10.1016/1074-7613(94)90084-1
  • Girtsman, T., Jaffar, Z., Ferrini, M., Shaw, P., Roberts, K., Natural Foxp3(+) regulatory T cells inhibit Th2 polarization but are biased toward suppression of Th17-driven lung inflammation (2010) J Leukoc Biol, 88, pp. 537-546. , http://dx.doi.org/10.1189/jlb.0110044
  • Kierszenbaum, F., Cuna, W.R., Beltz, L.A., Sztein, M.B., Trypanosomal immunosuppressive factor: a secretion product(s) of Trypanosoma cruzi that inhibits proliferation and IL-2 receptor expression by activated human peripheral blood mononuclear cells (1990) J Immunol, 144, pp. 4000-4004
  • Kierszenbaum, F., Majumder, S., Paredes, P., Tanner, M.K., Sztein, M.B., The Trypanosoma cruzi immunosuppressive factor (TIF) targets a lymphocyte activation event subsequent to increased intracellular calcium ion concentration and translocation of protein kinase C but previous to cyclin D2 and cdk4 mRNA accumulation (1998) Mol Biochem Parasitol, 92, pp. 133-145. , http://dx.doi.org/10.1016/S0166-6851(97)00240-5
  • Beltz, L.A., Sztein, M.B., Kierszenbaum, F., Novel mechanism for Trypanosoma cruzi-induced suppression of human lymphocytes. Inhibition of IL-2 receptor expression (1988) J Immunol, 141, pp. 289-294
  • Beltz, L.A., Sonnenfeld, G., Kierszenbaum, F., Inhibition by Trypanosoma cruzi of interferon-gamma production by mitogen-stimulated mouse spleen cells (1989) Int J Parasitol, 19, pp. 555-559. , http://dx.doi.org/10.1016/0020-7519(89)90086-6
  • Fiorentino, D.F., Zlotnik, A., Vieira, P., Mosmann, T.R., Howard, M., Moore, K.W., O'Garra, A., IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells (1991) J Immunol, 146, pp. 3444-3451
  • Taga, K., Tosato, G., IL-10 inhibits human T cell proliferation and IL-2 production (1992) J Immunol, 148, pp. 1143-1148
  • de Waal Malefyt, R., Yssel, H., de Vries, J.E., Direct effects of IL-10 on subsets of human CD4+ T cell clones and resting T cells. Specific inhibition of IL-2 production and proliferation (1993) J Immunol, 150, pp. 4754-4765
  • Reed, S.G., Brownell, C.E., Russo, D.M., Silva, J.S., Grabstein, K.H., Morrissey, P.J., IL-10 mediates susceptibility to Trypanosoma cruzi infection (1994) J Immunol, 153, pp. 3135-3140
  • Hunter, C.A., Ellis-Neyes, L.A., Slifer, T., Kanaly, S., Grunig, G., Fort, M., Rennick, D., Araujo, F.G., IL-10 is required to prevent immune hyperactivity during infection with Trypanosoma cruzi (1997) J Immunol, 158, pp. 3311-3316
  • Holscher, C., Mohrs, M., Dai, W.J., Kohler, G., Ryffel, B., Schaub, G.A., Mossmann, H., Brombacher, F., Tumor necrosis factor alphamediated toxic shock in Trypanosoma cruzi-infected interleukin 10-deficient mice (2000) Infect Immun, 68, pp. 4075-4083. , http://dx.doi.org/10.1128/IAI.68.7.4075-4083.2000
  • Alba Soto, C.D., Solana, M.E., Poncini, C.V., Pino-Martinez, A.M., Tekiel, V., Gonzalez-Cappa, S.M., Dendritic cells devoid of IL-10 induce protective immunity against the protozoan parasite Trypanosoma cruzi (2010) Vaccine, 28, pp. 7407-7413. , http://dx.doi.org/10.1016/j.vaccine.2010.08.105
  • Frevert, U., Schenkman, S., Nussenzweig, V., Stage-specific expression and intracellular shedding of the cell surface trans-sialidase of Trypanosoma cruzi (1992) Infect Immun, 60, pp. 2349-2360
  • Oppezzo, P., Obal, G., Baraibar, M.A., Pritsch, O., Alzari, P.M., Buschiazzo, A., Crystal structure of an enzymatically inactive trans-sialidase-like lectin from Trypanosoma cruzi: the carbohydrate binding mechanism involves residual sialidase activity (2011) Biochim Biophys Acta, 1814, pp. 1154-1161. , http://dx.doi.org/10.1016/j.bbapap.2011.04.012
  • Todeschini, A.R., Nunes, M.P., Pires, R.S., Lopes, M.F., Previato, J.O., Mendonca-Previato, L., DosReis, G.A., Costimulation of host T lymphocytes by a trypanosomal trans-sialidase: involvement of CD43 signaling (2002) J Immunol, 168, pp. 5192-5198. , http://dx.doi.org/10.4049/jimmunol.168.10.5192
  • Gao, W., Pereira, M.A., Trypanosoma cruzi trans-sialidase potentiates T cell activation through antigen-presenting cells: role of IL-6 and Bruton's tyrosine kinase (2001) Eur J Immunol, 31, pp. 1503-1512. , http://dx.doi.org/10.1002/1521-4141(200105)31:5<1503::AID-IMMU1503>3.0.CO;2-W
  • Fontanella, G.H., De Vusser, K., Laroy, W., Daurelio, L., Nocito, A.L., Revelli, S., Contreras, R., Immunization with an engineered mutant trans-sialidase highly protects mice from experimental Trypanosoma cruzi infection: a vaccine candidate (2008) Vaccine, 26, pp. 2322-2334. , http://dx.doi.org/10.1016/j.vaccine.2008.02.060
  • Costa, F., Franchin, G., Pereira-Chioccola, V.L., Ribeirao, M., Schenkman, S., Rodrigues, M.M., Immunization with a plasmid DNA containing the gene of trans-sialidase reduces Trypanosoma cruzi infection in mice (1998) Vaccine, 16, pp. 768-774. , http://dx.doi.org/10.1016/S0264-410X(97)00277-6
  • Bermejo, D.A., Jackson, S.W., Gorosito-Serran, M., Acosta-Rodriguez, E.V., Amezcua-Vesely, M.C., Sather, B.D., Singh, A.K., Rawlings, D.J., Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORgammat and Ahr that leads to IL-17 production by activated B cells (2013) Nat Immunol, 14, pp. 514-522. , http://dx.doi.org/10.1038/ni.2569
  • Tribulatti, M.V., Figini, M.G., Carabelli, J., Cattaneo, V., Campetella, O., Redundant and antagonistic functions of galectin-1, -3, and -8 in the elicitation of T cell responses (2012) J Immunol, 188, pp. 2991-2999. , http://dx.doi.org/10.4049/jimmunol.1102182
  • Burgos, J.M., Risso, M.G., Breniere, S.F., Barnabe, C., Campetella, O., Leguizamon, M.S., Differential distribution of genes encoding the virulence factor trans-sialidase along Trypanosoma cruzi discrete typing units (2013) PLoS One, 8. , http://dx.doi.org/10.1371/journal.pone.0058967
  • Padilla, A.M., Bustamante, J.M., Tarleton, R.L., CD8+ T cells in Trypanosoma cruzi infection (2009) Curr Opin Immunol, 21, pp. 385-390. , http://dx.doi.org/10.1016/j.coi.2009.07.006
  • Albareda, M.C., Olivera, G.C., Laucella, S.A., Alvarez, M.G., Fernandez, E.R., Lococo, B., Viotti, R., Postan, M., Chronic human infection with Trypanosoma cruzi drives CD4+ T cells to immune senescence (2009) J Immunol, 183, pp. 4103-4108. , http://dx.doi.org/10.4049/jimmunol.0900852
  • Albareda, M.C., De Rissio, A.M., Tomas, G., Serjan, A., Alvarez, M.G., Viotti, R., Fichera, L.E., Laucella, S.A., Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults (2013) PLoS Negl Trop Dis, 7. , http://dx.doi.org/10.1371/journal.pntd.0002575
  • Trocoli Torrecilhas, A.C., Tonelli, R.R., Pavanelli, W.R., da Silva, J.S., Schumacher, R.I., de Souza, W., Cunha e Silva, N., Manso Alves, M.J., Trypanosoma cruzi: parasite shed vesicles increase heart parasitism and generate an intense inflammatory response (2009) Microbes Infect, 11, pp. 29-39. , http://dx.doi.org/10.1016/j.micinf.2008.10.003
  • Redpath, S.A., Fonseca, N.M., Perona-Wright, G., Protection and pathology during parasite infection: IL-10 strikes the balance (2014) Parasite Immunol, 36, pp. 233-252. , http://dx.doi.org/10.1111/pim.12113
  • Salvador, R., Aridgides, D., PereiraPerrin, M., Parasite-derived neurotrophic factor/trans-sialidase of Trypanosoma cruzi links neurotrophic signaling to cardiac innate immune response (2014) Infect Immun, 82, pp. 3687-3696. , http://dx.doi.org/10.1128/IAI.02098-14
  • Steinfelder, S., Andersen, J.F., Cannons, J.L., Feng, C.G., Joshi, M., Dwyer, D., Caspar, P., Jankovic, D., The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1) (2009) J Exp Med, 206, pp. 1681-1690. , http://dx.doi.org/10.1084/jem.20082462
  • Everts, B., Perona-Wright, G., Smits, H.H., Hokke, C.H., van der Ham, A.J., Fitzsimmons, C.M., Doenhoff, M.J., Schramm, G., Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses (2009) J Exp Med, 206, pp. 1673-1680. , http://dx.doi.org/10.1084/jem.20082460

Citas:

---------- APA ----------
Díaz, P.R., Mucci, J., Meira, M.A., Bogliotti, Y., Musikant, D., Leguizamón, M.S. & Campetella, O. (2015) . Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells. Infection and Immunity, 83(5), 2099-2108.
http://dx.doi.org/10.1128/IAI.00031-15
---------- CHICAGO ----------
Díaz, P.R., Mucci, J., Meira, M.A., Bogliotti, Y., Musikant, D., Leguizamón, M.S., et al. "Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells" . Infection and Immunity 83, no. 5 (2015) : 2099-2108.
http://dx.doi.org/10.1128/IAI.00031-15
---------- MLA ----------
Díaz, P.R., Mucci, J., Meira, M.A., Bogliotti, Y., Musikant, D., Leguizamón, M.S., et al. "Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells" . Infection and Immunity, vol. 83, no. 5, 2015, pp. 2099-2108.
http://dx.doi.org/10.1128/IAI.00031-15
---------- VANCOUVER ----------
Díaz, P.R., Mucci, J., Meira, M.A., Bogliotti, Y., Musikant, D., Leguizamón, M.S., et al. Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells. Infect. Immun. 2015;83(5):2099-2108.
http://dx.doi.org/10.1128/IAI.00031-15