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In vivo infection by Trypanosoma cruzi: The conserved FLY domain of the gp85/trans-sialidase family potentiates host infection

Published online by Cambridge University Press:  02 November 2010

R. R. TONELLI
Affiliation:
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brasil
A. C. TORRECILHAS
Affiliation:
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brasil
J. F. JACYSYN
Affiliation:
Laboratório de Investigação Médica-LIM62-Hospital das Clínicas da Faculdade de Medicina daUniversidade de São Paulo, São Paulo, Brasil
M. A. JULIANO
Affiliation:
Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, Brasil
W. COLLI
Affiliation:
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brasil
M. J. M. ALVES*
Affiliation:
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brasil
*
*Corresponding author: Universidade de São Paulo, Av. Prof Lineu Prestes 748, 05508-900 São Paulo, Brasil. E-mail: mjmalves@iq.usp.br

Summary

Trypanosoma cruzi is a protozoan parasite that infects vertebrates, causing in humans a pathological condition known as Chagas’ disease. The infection of host cells by T. cruzi involves a vast collection of molecules, including a family of 85 kDa GPI-anchored glycoproteins belonging to the gp85/trans-sialidase superfamily, which contains a conserved cell-binding sequence (VTVXNVFLYNR) known as FLY, for short. Herein, it is shown that BALB/c mice administered with a single dose (1 μg/animal, intraperitoneally) of FLY-synthetic peptide are more susceptible to infection by T. cruzi, with increased systemic parasitaemia (2-fold) and mortality. Higher tissue parasitism was observed in bladder (7·6-fold), heart (3-fold) and small intestine (3·6-fold). Moreover, an intense inflammatory response and increment of CD4+ T cells (1·7-fold) were detected in the heart of FLY-primed and infected animals, with a 5-fold relative increase of CD4+CD25+FoxP3+ T (Treg) cells. Mice treated with anti-CD25 antibodies prior to infection, showed a decrease in parasitaemia in the FLY model employed. In conclusion, the results suggest that FLY facilitates in vivo infection by T. cruzi and concurs with other factors to improve parasite survival to such an extent that might influence the progression of pathology in Chagas’ disease.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2010

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References

REFERENCES

Aliberti, J. C. S., Machado, F. S., Souto, J. T., Campanelli, A. P., Teixeira, M. M., Gazzinelli, R. T. and Silva, J. S. (1999). β-Chemokines enhance parasite uptake and promote nitric oxide-dependent microbiostatic activity in murine inflammatory macrophages infected with Trypanosoma cruzi. Infection and Immunity 67, 48194826.CrossRefGoogle ScholarPubMed
Alvarez, M. G., Postan, M., Weatherly, D. B., Albareda, M. C., Sidney, J., Sette, A., Olivera, C., Armenti, A. H., Tarleton, R. L. and Laucella, S. A. (2008). HLA class I-T cell epitopes from trans-sialidase proteins reveal functionally distinct subsets of CD8+ T cells in chronic Chagas´ disease. Plos Neglected Tropical Diseases 2, e288.CrossRefGoogle ScholarPubMed
Araújo, F., Gomes, J., Rocha, M., Williams-Blangero, S., Pinheiro, V., Morato, M. and Correa-Oliveira, R. (2007). Potential role of CD4+CD25+-high regulatory T cells in morbidity in Chagas’ disease. Frontiers in Bioscience 12, 27972806.CrossRefGoogle Scholar
Belkaid, Y., Piccirillo, C. A., Mendez, S., Shevach, E. M. and Sacks, D. L. (2002 a). CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature, London 420, 502507. doi: 10.1038/nature01152nature01152 [pii].CrossRefGoogle ScholarPubMed
Belkaid, Y. and Rouse, B. T. (2005). Natural regulatory T cells in infectious disease. Nature Immunology 6, 353360. doi: ni1181 [pii]10.1038/ni1181[a1].CrossRefGoogle ScholarPubMed
Belkaid, Y., Von Stebut, E., Mendez, S., Lira, R., Caler, E., Bertholet, S., Udey, M. C. and Sacks, D. (2002 b). CD8+ T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major. Journal of Immunology 168, 39924000.CrossRefGoogle ScholarPubMed
Brener, Z. (1962). Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi. Revista do Instituto de Medicina Tropical de Sao Paulo 4, 389396.Google ScholarPubMed
Burns, J. M. Jr., Shreffler, W. G., Rosman, D. E., Sleath, P. R., March, C. J. and Reed, S. G. (1992). Identification and synthesis of a major conserved antigenic epitope of Trypanosoma cruzi. Proceedings of the National Academy of Sciences, USA, 89, 12391243.CrossRefGoogle Scholar
Buschiazzo, A., Amaya, M., Cremona, M., Frasch, A. and Alzari, P. (2002). The crystal structure and mode of action of trans-sialidase, a key enzyme in Trypanosoma cruzi pathogenesis. Molecular Cell 10, 757768.CrossRefGoogle ScholarPubMed
Chen, G., Liu, J., Wang, Q. H., Wu, Y., Feng, H., Zheng, W., Guo, S. Y., Li, D. M., Wang, J. C. and Cao, Y. M. (2009). Effects of CD4+CD25+Foxp3+ regulatory T cells on early Plasmodium yoelii 17XL infection in BALB/c mice. Parasitology 136, 11071120.CrossRefGoogle ScholarPubMed
Chuenkova, M. and Pereira, M. (1995). Trypanosoma cruzi trans-sialidase: enhancement of virulence in a murine model of Chagas’ disease. Journal of Experimental Medicine 181, 16931703.CrossRefGoogle Scholar
Chuenkova, M. and Pereira, M. (2001). The T. cruzi trans-sialidase induces PC12 cell differentiation via MAPK/ERK pathway. Neuroreport 12, 37153718.CrossRefGoogle Scholar
Collison, L. W., Pillai, M. R., Chaturvedi, V. and Vignali, D. A. A. (2009). Regulatory T cell suppression is potentiated by target T cells in a Cell contact, IL35- and IL10-dependent manner. Journal of Immunology 182 ,61216128.CrossRefGoogle Scholar
Curotto de Lafaille, M. and Lafaille, J. (2009). Natural and adaptive Foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 30, 626635.CrossRefGoogle ScholarPubMed
Dias, W., Fajardo, F., Graca-Souza, A., Freire-de-Lima, L., Vieira, F., Girard, M., Bouteille, B., Previato, J., Mendonca-Previato, L. and Todeschini, A. (2008). Endothelial cell signalling induced by trans-sialidase from Trypanosoma cruzi. Cell Microbiology 10, 8899.Google ScholarPubMed
El-Sayed, N. M., Myler, P. J., Bartholomeu, D. C., Nilsson, D., Aggarwal, G., Tran, A.-N., Ghedin, E., Worthey, E. A., Delcher, A. L., Blandin, G., Westenberger, S. J., Caler, E., Cerqueira, G. C., Branche, C., Haas, B., Anupama, A., Arner, E., Aslund, L., Attipoe, P., Bontempi, E., Bringaud, F., Burton, P., Cadag, E., Campbell, D. A., Carrington, M., Crabtree, J., Darban, H., da Silveira, J. F., de Jong, P., Edwards, K., Englund, P. T., Fazelina, G., Feldblyum, T., Ferella, M., Frasch, A. C., Gull, K., Horn, D., Hou, L., Huang, Y., Kindlund, E., Klingbeil, M., Kluge, S., Koo, H., Lacerda, D., Levin, M. J., Lorenzi, H., Louie, T., Machado, C. R., McCulloch, R., McKenna, A., Mizuno, Y., Mottram, J. C., Nelson, S., Ochaya, S., Osoegawa, K., Pai, G., Parsons, M., Pentony, M., Pettersson, U., Pop, M., Ramirez, J. L., Rinta, J., Robertson, L., Salzberg, S. L., Sanchez, D. O., Seyler, A., Sharma, R., Shetty, J., Simpson, A. J., Sisk, E., Tammi, M. T., Tarleton, R., Teixeira, S., Van Aken, S., Vogt, C., Ward, P. N., Wickstead, B., Wortman, J., White, O., Fraser, C. M., Stuart, K. D. and Andersson, B. (2005). The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas´ Disease. Science 309, 409415.CrossRefGoogle ScholarPubMed
Freire-de-Lima, L., Alisson-Silva, F., Carvalho, S. T., Takiya, C. M., Rodrigues, M. M., DosReis, G. A., Mendonca-Previato, L., Previato, J. O. and Todeschini, A. R. (2010). Trypanosoma cruzi subverts host cell sialylation and may compromise antigen-specific CD8+ T cell responses. Journal of Biological Chemistry 285, 1338813396. doi: 10.1074/jbc.M109.096305.CrossRefGoogle ScholarPubMed
Freire-de-Lima, C., Nascimento, D., Soares, M., Bozza, P., Castro-Faria-Neto, H., de Mello, F., DosReis, G. and Lopes, M. (2000). Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages. Nature, London 403, 199203.CrossRefGoogle ScholarPubMed
Giordano, R., Fouts, D. L., Tewari, D. S., Colli, W., Manning, J. E. and Alves, M. J. M. (1999). Cloning of a surface membrane glycoprotein specific for the infective form of Trypanosoma cruzi having adhesive properties to laminin. Journal of Biological Chemistry 274, 34613468.CrossRefGoogle ScholarPubMed
Gonçalves, M. F., Umezawa, E. S., Katzin, A. M., de Souza, W., Alves, M. J., Zingales, B. and Colli, W. (1991). Trypanosoma cruzi: shedding of surface antigens as membrane vesicles. Experimental Parasitology 72, 4353.CrossRefGoogle ScholarPubMed
Hisaeda, H., Maekawa, Y., Iwakawa, D., Okada, H., Himeno, K., Kishihara, K., Tsukumo, S. and Yasutomo, K. (2004). Escape of malaria parasites from host immunity requires CD4+ CD25+ regulatory T cells. Nature Medicine 10, 2930. doi: 10.1038/nm975nm975 [pii].CrossRefGoogle ScholarPubMed
Kotner, J. and Tarleton, R. (2007). Endogenous CD4+ CD25+ regulatory T cells have a limited role in the control of Trypanosoma cruzi infection in mice. Infection and Immunity 75, 861869. doi: 10.1128/iai.01500-06.CrossRefGoogle ScholarPubMed
Lambert, H., Hitziger, N., Dellacasa, I., Svensson, M. and Barragan, A. (2006). Induction of dendritic cell migration upon Toxoplasma gondii infection potentiates parasite dissemination. Cell Microbiology 8, 16111623.CrossRefGoogle ScholarPubMed
Leguizamon, M. S., Mocetti, E., Garcia Rivello, H., Argibay, P. and Campetella, O. (1999). Trans-sialidase from Trypanosoma cruzi induces apoptosis in cells from the immune system in vivo. Journal of Infectious Diseases 180, 13981402.CrossRefGoogle ScholarPubMed
Lopez, M., Huynh, C., Andrade, L. O., Pypaert, M. and Andrews, N. W. (2002). Role for sialic acid in the formation of tight lysosome-derived vacuoles during Trypanosoma cruzi invasion. Molecular and Biochemical Parasitology 119, 141145.CrossRefGoogle ScholarPubMed
Magdesian, M. H., Giordano, R., Ulrich, H., Juliano, M. A., Juliano, L., Schumacher, R. I., Colli, W. and Alves, M. J. M. (2001). Infection by Trypanosoma cruzi. Identification of a parasite ligand and its host cell receptor. Journal of Biological Chemistry 276, 1938219389.CrossRefGoogle ScholarPubMed
Magdesian, M., Tonelli, R., Fessel, M., Silveira, M., Schumacher, R., Linden, R., Colli, W. and Alves, M. (2007). A conserved domain of the gp85/trans-sialidase family activates host cell extracellular signal-regulated kinase and facilitates Trypanosoma cruzi infection. Experimental Cell Research 313, 210218.CrossRefGoogle ScholarPubMed
Mariano, F. S., Gutierrez, F. R., Pavanelli, W. R., Milanezi, C. M., Cavassani, K. A., Moreira, A. P., Ferreira, B. R., Cunha, F. Q., Cardoso, C. R. and Silva, J. S. (2008). The involvement of CD4+CD25+ T cells in the acute phase of Trypanosoma cruzi infection. Microbes and Infection 10, 825833.CrossRefGoogle ScholarPubMed
Marroquin-Quelopana, M., Oyama, S. Jr, Pertinhez, T. A., Spisni, A., Juliano, M. A., Juliano, L., Colli, W. and Alves, M. J. M. (2004). Modeling the Trypanosoma cruzi Tc85-11 protein and mapping the laminin-binding site. Biochemical and Biophysical Research Communications 325, 612618.CrossRefGoogle ScholarPubMed
Martin, D. L., Weatherly, D. B., Laucella, S. A., Cabinian, M. A., Crim, M. T., Sullivan, S., Heiges, M., Craven, S. H., Rosenberg, C. S., Collins, M. H., Sette, A., Postan, M. and Tarleton, R. L. (2006). CD8+ T-Cell responses to Trypanosoma cruzi are highly focused on strain-variant trans-sialidase epitopes. Plos Pathogens, 2, e77.CrossRefGoogle ScholarPubMed
Murai, M., Turovskaya, O., Kim, G., Madan, R., Karp, C., Cheroutre, H. and Kronenberg, M. (2009). Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nature Immunology 10, 11781184.CrossRefGoogle ScholarPubMed
Neira, I., Silva, F. A., Cortez, M. and Yoshida, N. (2003). Involvement of Trypanosoma cruzi metacyclic trypomastigote surface molecule gp82 in adhesion to gastric mucin and invasion of epithelial cells. Infection and Immunity 71, 557561.CrossRefGoogle ScholarPubMed
Patel, L., Zaro, J. and Shen, W. (2007 a). Cell penetrating peptides: intracellular pathways and pharmaceutical perspectives. Pharmaceutical Research 24, 19771992.CrossRefGoogle ScholarPubMed
Patel, L. N., Zaro, J. L. and Shen, W. C. (2007 b). Cell penetrating peptides: intracellular pathways and pharmaceutical perspectives. Pharmaceutical Research 24, 19771992. doi: 10.1007/s11095-007-9303-7CrossRefGoogle ScholarPubMed
Pitcovsky, T. A., Mucci, J., Alvarez, P., Susana Leguizamón, M., Burrone, O., Alzari, P. M. and Campetella, O. E. (2001). Epitope mapping of trans-sialidase from Trypanosoma cruzi reveals the presence of several cross-reactive determinants. Infection and Immunity 69, 18691875.CrossRefGoogle ScholarPubMed
Previato, J., Andrade, A., Pessolani, M. and Mendonca-Previato, L. (1985). Incorporation of sialic acid into Trypanosoma cruzi macromolecules. A proposal for a new metabolic route. Molecular and Biochemical Parasitology 16, 8596.CrossRefGoogle ScholarPubMed
Reed, S., Brownell, C., Russo, D., Silva, J., Grabstein, K. and Morrissey, P. (1994). IL-10 mediates susceptibility to Trypanosoma cruzi infection. Journal of Immunology 153, 31353140.CrossRefGoogle ScholarPubMed
Ribeirão, M., Pereira-Chioccola, V. L., Renia, L., Augusto Fragata, F. A., Schenkman, S. and Rodrigues, M. M. (2000). Chagasic patients develop a type 1 immune response to Trypanosoma cruzi trans-sialidase. Parasite Immunology 22, 4953.CrossRefGoogle ScholarPubMed
Rouse, B. T. and Suvas, S. (2004). Regulatory cells and infectious agents: detentes cordiale and contraire. Journal of Immunology 173, 22112215. doi: 173/4/2211 [pii].CrossRefGoogle ScholarPubMed
Rubin-de-Celis, S. S., Uemura, H., Yoshida, N. and Schenkman, S. (2006). Expression of trypomastigote trans-sialidase in metacyclic forms of Trypanosoma cruzi increases parasite escape from its parasitophorous vacuole. Cellular Microbiology 8, 18881898.CrossRefGoogle ScholarPubMed
Sales, P. A., Golgher, D., Oliveira, R. V., Vieira, V., Arantes, R. M., Lannes-Vieira, J. and Gazzinelli, R. T. (2008). The regulatory CD4+CD25+ T cells have a limited role on pathogenesis of infection with Trypanosoma cruzi. Microbes and Infection 10, 680688.CrossRefGoogle ScholarPubMed
Santori, F. R., Paranhos-Bacalla, G., Franco DA Silveira, J., Yamauchi, L., Araya, J. and Yoshida, N. (1996). A recombinant protein based on the Trypanosoma cruzi metacyclic trypomastigote 82-kilodalton antigen that induces and effective immune response to acute infection. Infection and Immunity 64, 10931099.CrossRefGoogle Scholar
Sathler-Avelar, R., Vitelli-Avelar, D., Teixeira-Carvalho, A. and Martins-Filho, O. (2009). Innate immunity and regulatory T-cells in human Chagas disease: what must be understood? Memorias do Instituto Oswaldo Cruz 104 (Suppl. 1), 246251.CrossRefGoogle ScholarPubMed
Schenkman, S., Jiang, M. S., Hart, G. W. and Nussenzweig, V. (1991). A novel cell surface trans-sialidase of Trypanosoma cruzi generates a stage-specific epitope required for invasion mammalian cells. Cell 65, 11171125.CrossRefGoogle ScholarPubMed
Scholzen, A., Mittag, D., Rogerson, S., Cooke, B. and Plebanski, M. (2009). Plasmodium falciparum-mediated induction of human CD25+Foxp3+ CD4+ T cells is independent of direct TCR stimulation and requires IL-2, IL-10 and TGFβ. PLoS Pathology 5, e1000543.CrossRefGoogle ScholarPubMed
Singh, A., Buscaglia, C., Wang, Q., Levay, A., Nussenzweig, D., Walker, J., Winzeler, E., Fujii, H., Fontoura, B. and Nussenzweig, V. (2007). Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite. Cell 131, 492504.CrossRefGoogle ScholarPubMed
Tarleton, R. L. (2007). Immune system recognition of Trypanosoma cruzi. Current Opinion in Immunology 19, 430434.CrossRefGoogle ScholarPubMed
Todeschini, A. R., Nunes, M. P., Pires, R. S., Lopes, M. F., Previato, J. O., Mendonca-Previato, L. and DosReis, G. A. (2002). Costimulation of host T lymphocytes by a trypanosomal trans-sialidase: involvement of CD43 signaling. Journal of Immunology 168, 51925198.CrossRefGoogle Scholar
Torrecilhas, A. C. T., Tonelli, R. R., Pavanelli, W. R., Da Silva, J. S., Schumacher, R. I., de Souza, W., Cunha-e-Silva, N., Abrahamsohn, I. A., Colli, W. and Alves, M. J. M. (2009). Trypanosoma cruzi: parasite shed vesicles increase heart parasitism and generate an intense inflammatory response. Microbes and Infection 11, 2939.CrossRefGoogle Scholar
Yamauchi, L., Aliberti, J., Baruffi, M., Portela, R., Rossi, M., Gazzinelli, R., Mineo, J. and Silva, J. (2007). The binding of CCL2 to the surface of Trypanosoma cruzi induces chemo-attraction and morphogenesis. Microbes and Infection 9, 111118.CrossRefGoogle Scholar
Yoshida, N., Dorta, M. L., Ferreira, A. T., Oshiro, M. E., Mortara, R. A., Acosta-Serrano, A. and Favoreto, S. Junior (1997). Removal of sialic from mucin-like surface molecules of Trypanosoma cruzi metacyclic trypomastigotes enhances parasite-host cell interaction. Molecular and Biochemical Parasitology 84, 5767.CrossRefGoogle ScholarPubMed