Angiotensin-converting enzyme limits inflammation elicited by Trypanosoma cruzi cysteine proteases: A peripheral mechanism regulating adaptive immunity via the innate kinin pathway

Biological Chemistry

Volumn 389, Issue 8, 2008, Pages 1015-1024

  Scharfstein, Julio ^a   Monteiro, Ana Carolina ^a   Schmitz, Veronica ^a   Svensjö, Erik ^a  

^a FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

Author keywords

Angiotensin; Bradykinin; Cruzipain; Dendritic cells; Trypanosoma cruzi

Indexed keywords

BRADYKININ; BRADYKININ B2 RECEPTOR; CRUZIPAIN; CYSTEINE PROTEINASE; DIPEPTIDYL CARBOXYPEPTIDASE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; G PROTEIN COUPLED RECEPTOR; GAMMA INTERFERON; KININ;

ADAPTIVE IMMUNITY; CELL ACTIVATION; CELL MATURATION; CHAGAS DISEASE; CONFERENCE PAPER; CORRELATION ANALYSIS; CYTOKINE PRODUCTION; DENDRITIC CELL; EFFECTOR CELL; ENZYME ACTIVITY; ENZYME DEGRADATION; ENZYME MECHANISM; ENZYME RELEASE; ENZYME STRUCTURE; HOST PARASITE INTERACTION; HUMAN; IMMUNOSTIMULATION; INFLAMMATION; INNATE IMMUNITY; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; TH1 CELL; TRYPANOSOMA CRUZI; TRYPANOSOMIASIS;

ADAPTATION, BIOLOGICAL; ANIMALS; CYSTEINE ENDOPEPTIDASES; HUMANS; IMMUNITY, INNATE; KININS; PEPTIDYL-DIPEPTIDASE A; TRYPANOSOMA CRUZI;

MUS; PROTOZOA; TRYPANOSOMA CRUZI;

EID: 50849124779     PISSN: 14316730     EISSN: 14374315     Source Type: Journal    
DOI: 10.1515/BC.2008.126     Document Type: Conference Paper

References (90)

1. Aliberti, J., Viola, J.P., Vieira-de-Abreu, A., Bozza, P.T., Sher, A., and Scharfstein, J. (2003). Cutting edge: bradykinin induces IL-12 production by dendritic cells: a danger signal that drives Th1 polarization. J. Immunol. 170, 5349-5353.
2. Andrade, L.O. and Andrews, N.W. (2004). Lysosomal fusion is essential for the retention of Trypanosoma cruzi inside host cells. J. Exp. Med. 200, 1135-1143.
3. Andrade, S.G., Pimentel, A.R., de Souza, M.M., and Andrade, Z.A. (2000). Interstitial dendritic cells of the heart harbor Trypanosoma cruzi antigens in experimentally infected dogs: importance for the pathogenesis of chagasic myocarditis. Am. J. Trop. Med. Hyg. 63, 64-70.
4. Aparicio, I.M., Scharfstein, J., and Lima, A.P. (2004). A new cruzipain-dependent pathway of human cell invasion by Trypanosoma cruzi requiring trypomastigote membranes. Infect. Immun. 72, 5892-5902.
5. Apetoh, L., Ghiringhelli, F., Tesniere, A., Obeid, M., Ortiz, C., Criollo, A., Mignot, G., Maiuri, C.M., Ullrich, E., Saulnier, P., et al. (2007). Toll-like receptor 4-dependent contribution of the immune system to anti-cancer chemotherapy and radiotherapy. Nat. Med. 13, 1050-1059.
6. Arnholdt, A.C., Piuvezam, M.R., Russo, D.M., Lima, A.P., Pedrosa, R.C., Reed, S.G., and Scharfstein, J. (1993). Analysis and partial epitope mapping of human T cell responses to Trypanosoma cruzi cysteinyl proteinase. J. Immunol. 151, 3171-3179.
7. Bafica, A., Santiago, H.C., Goldszmid, R., Ropert, C., Gazzinelli, R.T., and Sher, A. (2006). Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection. J. Immunol. 177, 3515-3519.
8. 2+ and cell migration. J. Leukoc. Biol. 81, 1445-1454.
9. Bhoola, K.D., Figueroa, C.D., and Worthy, K. (1992). Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol. Rev. 44, 1-80.
10. Burleigh, B.A. and Woolsey, A.M. (2002). Cell signalling and Trypanosoma cruzi invasion. Cell Microbiol. 4, 701-711.
11. Caler, E.V., Vaena de Avalos, S., Haynes, P.A., Andrews, N.W., and Burleigh, B.A. (1998). Oligopeptidase B-dependent signaling mediates host cell invasion by Trypanosoma cruzi. EMBO J. 17, 4975-4986.
12. Caler, E.V., Chakrabarti, S., Fowler K.T., Rao, S., and Andrews, N.W. (2001). The exocytosis-regulatory protein synaptotagmin VII mediates cell invasion by Trypanosoma cruzi. J. Exp. Med. 193, 1097-1104.
13. Calixto, J.B., Medeiros, R., Fernandes, E.S., Ferreira, J., Cabrini, D.A., and Campos, M.M. (2004). Kinin B1 receptors: key G-protein-coupled receptors and their role in inflammatory and painful processes. Br. J. Pharmacol. 143, 803-818.
14. Cazzulo, J.J. (2002). Proteinases of Trypanosoma cruzi: potential targets for the chemotherapy of Chagas disease. Curr. Top. Med. Chem. 2, 1261-1271.
15. Costa, V.M., Torres, K.C., Mendonça, R.Z., Gresser, I., Gollob, K.J., and Abrahamsohn, I.A. (2006). Type I IFNs stimulate nitric oxide production and resistance to Trypanosoma cruzi infection. J. Immunol. 177, 3193-3200.
16. Cunha, T.M., Verri, W.A. Jr, Fukada, S.Y., Guerrero, A.T., Santo-domingo-Garzón, T., Poole, S., Parada, C.A., Ferreira, S.H., and Cunha, F.Q. (2007). TNF-α and IL-1β mediate inflammatory hypernociception in mice triggered by B1 but not B2 kinin receptor. Eur. J. Pharmacol. 573, 221-229.
17. Danilov, S.M., Sadovnikova, E., Scharenborg, N., Balyasnikova, I.V., Svinareva, D.A., Semikina, E.L., Parovichnikova, E.N., Savchenko, V.G., and Adema, G.J. (2003). Angiotensin converting enzyme (CD143) is abundantly expressed by dendritic cells and discriminates human monocyte-derived dendritic cells from acute myeloid leukemia-derived dendritic cells. Exp. Hematol. 31, 1301-1309.
18. Del Nery, E., Juliano, M.A., Lima, A.P., Scharfstein, J., and Juliano, L. (1997). Kininogenase activity by the major cysteinyl proteinase (cruzipain) from Trypanosoma cruzi. J. Biol. Chem. 272, 25713-25718.
19. Doyle, P.S., Zhou, Y.M., Engel, J.C., and McKerrow, J.H. (2007). A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection. Antimicrob. Agents Chemother. 51, 3932-3939.
20. dos Reis, F.C., Judice, W.A., Juliano, M.A., Juliano, L., Scharfstein, J., and Lima, A.P. (2006). The substrate specificity of cruzipain 2, a cysteine protease isoform from Trypanosoma cruzi. FEMS Microbiol. Lett. 259, 215-220.
21. 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., et al. (2005). The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science 309, 409-415.
22. Engman, D.M. and Leon, J.S. (2002). Pathogenesis of Chagas heart disease: role of autoimmunity. Acta Trop. 81, 123-132.
23. Figueiredo da Silva, A.A., de Carvalho Vieira, L., Krieger, M.A., Goldenberg, S., Zanchin, N.I., and Guimarães, B.G. (2007). Crystal structure of chagasin, the endogenous cysteineprotease inhibitor from Trypanosoma cruzi. J. Struct. Biol. 157, 416-423.
24. + epitopes recognized by T cells from chronically Trypanosoma cruzi-infected patients. Microbes Infect. 7, 688-697.
25. Freire-de-Lima, C.G., Nascimento, D.O., Soares, M.B., Bozza, P.T., Castro-Faria-Neto, H.C., de Mello, F.G., Dos Reis, G.A., and Lopes, M.F. (2000). Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages. Nature 403, 199-203.
26. Gillmor, S.A., Craik, C.S., and Fletterick, R.J. (1997). Structural determinants of specificity in the cysteine protease cruzain. Protein Sci. 6, 1603-1611.
27. Guiñazú, N., Pellegrini, A., Carrera-Silva, E.A., Aoki, M.P., Cabanillas, A.M., Gìronés, N., Fresno, M., Cano, R., and Gea, S. (2007). Immunisation with a major Trypanosoma cruzi antigen promotes pro-inflammatory cytokines, nitric oxide production and increases TLR2 expression. Int. J. Parasitol. 37, 1243-1254.
28. Grakoui, A., Bromley, S.K., Sumen, C., Davis, M.M., Shaw, A.S., Allen, P.M., and Dustin, M.L. (1999). The immunological synapse: a molecular machine controlling T cell activation. Science 285, 221-227.
29. Hawiger, D., Inaba, K., Dorsett, Y., Guo, M., Mahnke, K., Rivera, M., Ravetch, J.V., Steinman, R.M., and Nussenzweig, M.C. (2001). Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194, 769-779.
30. Hawlisch, H., Wills-Karp, M., Karp, C.L., and Köhl, J. (2004). The anaphylatoxins bridge innate and adaptive immune responses in allergic asthma. Mol. Immunol. 41, 123-131.
31. Hellman, U., Wernstedt, C., and Cazzulo, J.J. (1991). Self-proteolysis of the cysteine proteinase, cruzipain, from Trypanosoma cruzi gives a major fragment corresponding to its carboxy-terminal domain. Mol. Biochem. Parasitol. 44, 15-21.
32. Herwald, H., Hasan, A.A., Godovac-Zimmermann, J., Schmaier, A.H., and Müller-Esterl, W. (1995). Identification of an endothelial cell binding site on kininogens' domain. J. Biol. Chem. 270, 14634-14642.
33. Herwald, H., Collin, M., Müller-Esterl, W., and Björck, L. (1996). Streptococcal cysteine proteinase releases kinins: a virulence mechanism. J. Exp. Med. 184, 665-673.
34. Imamura, T., Pike, R.N., Potempa, J., and Travis J. (1994). Pathogenesis of periodontitis: a major arginine-specific cysteine proteinase from Porphyromonas gingivalis induces vascular permeability enhancement through activation of the kallikrein/kinin pathway. J. Clin. Invest. 94, 361-367.
35. Imamura, T., Tanase, S., Szmyd, G., Kozik, A., Travis, J., and Potempa, J. (2005). Induction of vascular leakage through release of bradykinin and a novel kinin by cysteine proteinases from Staphylococcus aureus. J. Exp. Med. 201, 1669-1676.
36. Inohara, N. and Nuñez, G. (2003). NODs: intracellular proteins involved in inflammation and apoptosis. Nat. Rev. Immunol. 3, 371-382.
37. Koga, R., Hamano, S., Kuwata, H., Atarashi, K., Ogawa, M., Hisaeda, H., Yamamoto, M., Akira, S., Himeno, K., Matsumoto, M., and Takeda, K. (2006). TLR-dependent induction of IFN-β mediates host defense against Trypanosoma cruzi. J. Immunol. 177, 7059-7066.
38. Kosec, G., Avarez, V., and Cazzulo, J.J. (2006). Cysteine proteinases of Trypanosoma cruzi: from digestive enzymes to programmed cell death mediators. Biocell 30, 479-490.
39. Kozik, A., Moore, R.B., Potempa, J., Imamura, T., Rapala-Kozik, M., and Travis, J. (1998). A novel mechanism for bradykinin production at inflammatory sites. Diverse effects of a mixture of neutrophil elastase and mast cell tryptase versus tissue and plasma kallikreins on native and oxidized kininogens. J. Biol. Chem. 273, 33224-33229.
40. Leeb-Lundberg, L.M., Marceau, F., Müller-Esterl, W., Pettibone, D.J., and Zuraw, B.L. (2005). International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol. Rev. 57, 27-77.
41. LeibundGut-Landman, S., Gross, O., Robinson, M.J., Osório, F., Slack, E.C., Tsoni, S.V., Schweighoffer, E., Tybulewicz, V., Brown, G.D., Ruland, J., and Reis e Sousa, C. (2007). Syk-and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat. Immunol. 8, 630-638.
42. Leite, M.F., Moyer, M.S., and Andrews, N.W. (1998). Expression of the mammalian calcium signaling response to Trypanosoma cruzi in Xenopus laevis oocytes. Mol. Biochem. Parasitol. 92, 1-13.
43. Lima, A.P., Scharfstein, J., Storer, A.C., and Ménard, R. (1992). Temperature-dependent substrate inhibition of the cysteine proteinase (GP57/51) from Trypanosoma cruzi. Mol. Biochem. Parasitol. 56, 335-338.
44. Lima, A.P., Reis, F.C.G., Serveau, C., Lalmanach, G., Juliano, L., Ménard, R., Vernet, T., Thomas, D.Y., Storer, A.C., and Scharfstein, J. (2001). Cysteine protease isoforms from Trypanosoma cruzi, cruzipain 2 and cruzain, present different substrate preference and susceptibility to inhibitors. Mol. Biochem. Parasitol. 114, 41-52.
45. Lima, A.P., Almeida, I.L., Tersariol, I., Lalmanach, G., Juliano, L, Ménard, R., Vernet, T., Thomas, D.Y., Storer, A.C., and Scharfstein, J. (2002). Heparan sulfate modulates kinin release by Trypanosoma cruzi through the activity of cruzipain. J. Biol. Chem. 277, 5875-5881.
46. Lindquist, R.L., Shakhar, G., Dudziak, D., Wardemann, H., Eisenreich, T., Dustin, M.L., and Nussenzweig, M.C. (2004). Visualizing dendritic cell networks in vivo. Nat. Immunol. 5, 243-250.
47. Ljunggren, A., Redzynia, I., Alvarez-Fernandez, M., Abrahamson, M., Mort, J.S., Krupa, J.C., Jaskolski, M., and Bujacz, G. (2007). Crystal structure of the parasite protease inhibitor chagasin in complex with a host target cysteine protease. J. Mol. Biol. 371, 137-153.
48. Marceau, F. and Bachvarov, D.R. (1998). Kinin receptors. Clin. Rev. Allergy Immunol. 6, 385-401.
49. Matzinger, P. (2002). The danger model: a renewed sense of self. Science 296, 301-305.
50. McGrath, M.E., Eakin, A.E., Engel, J.C., McKerrow, J.H., Craik, C.S., and Fletterick, R.J. (1995). The crystal structure of cruzain: a therapeutic target for Chagas' disease. J. Mol. Biol. 247, 251-259.
51. Medzhitov, R., Preston-Hurlburt, P., and Janeway, C.A. Jr. (1997). A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394-396.
52. Meirelles, M.N., Juliano, L., Carmona, E., Silva, S.G., Costa, E.M., Murta, A.C., and Scharfstein, J. (1992). Inhibitors of the major cysteinyl proteinase (GP57/51) impair host cell invasion and arrest the intracellular development of Trypanosoma cruzi in vitro. Mol. Biochem. Parasitol. 52, 175-184.
53. Mendonça-Previato, L., Gorin, P.A., Braga, A.F., Scharfstein, J., and Previato, J.O. (1983). Chemical structure and antigenic aspects of complexes obtained from epimastigotes of Trypanosoma cruzi. Biochemistry 22, 4980-4987.
54. Monteiro, A.C.S., Abrahamson, M., Lima, A.P., Vannier-Santos, M.A., and Scharfstein, J. (2001). Identification, characterization and localization of chagasin, a tight-binding cysteine proteinase inhibitor in Trypanosoma cruzi. J. Cell Sci. 114, 3933-3942.
55. Monteiro, A.C.S., Schmitz, V., Svensjö, E., Gazzinelli, R.T., Almeida, I.C., Todorov, A., de Arruda, L.B., Torrecilhas, A.C., Pesquero, J.B., Morrot, A., et al. (2006). Cooperative activation of TLR2 and bradykinin B2 receptor is required for induction of type-1 immunity in mouse model of subcutaneous infection by Trypanosoma cruzi. J. Immunol. 177, 5325-5335.
56. Monteiro, A.C., Schmitz, V., Morrot, A., de Arruda, L.B., Nagajyothi, F., Granato, A., Pesquero, J.B., Müller-Esterl, W., Tanowitz, H.B., and Scharfstein, J. (2007). Bradykinin B2 receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses. PLoS Pathog. 11, 1730-1744.
57. Murta, A.C., Persechini, P.M., Souto-Padron, T., de Souza, W., Guimarães, J.A., and Scharfstein, J. (1990). Structural and functional identification of GP57/51 antigen of Trypanosoma cruzi as a cysteine proteinase. Mol. Biochem. Parasitol. 43, 27-38.
58. Nataraj, C., Oliverio, M.I., Mannon, R.B., Mannon, P.J., Audoly, L.P., Amuchastegui, C.S., Ruiz, P., Smithies, O., and Coffman, T.M. (1999). Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway. J. Clin. Invest. 104, 1693-1701.
59. Parkin, E.T., Turner, A.J., and Hooper, N.M. (2004). Secretase-mediated cell surface shedding of the angiotensin-converting enzyme. Protein Pept. Lett. 11, 423-432.
60. Peiser, M., Koeck, J., Kirschning, C.J., Wittig, B., and Wanner, R. (2008). Human Langerhans cells selectively activated via Toll-like receptor 2 agonists acquire migratory and CD4q T cell stimulatory capacity. J. Leukoc. Biol. 83, 1118-1127.
61. Renné, T., Dedio, J., David, G., and Müller-Esterl, W. (2000). High molecular weight kininogen utilizes heparan sulfate proteoglycans for accumulation on endothelial cells. J. Biol. Chem. 275, 33688-33696.
62. Rocha e Silva, M., Beraldo, W.T., and Rosenfeld, G. (1949). Bradykinin, a hypotensive and smooth muscle stimulating factor released from plasma globulin by snake venoms and by trypsin. Am. J. Physiol. 156, 261-273.
63. Ropert, C. and Gazzinelli, R.T. (2007). Innate recognition, cell signaling and proinflammatory responses during infection with Trypanosoma cruzi. In: Protozoans in Macrophages, E.Y. Denkers and R.T. Gazzinelli, eds. (Austin, USA: Landes Biosciences), pp. 49-66.
64. Roush, W.R., Cheng, J., Knapp-Reed, B., Alvarez-Hernandez, A., McKerrow, J.H., Hansell, E., and Engel, J.C. (2001). Potent second generation vinyl sulfonamide inhibitors of the trypanosomal cysteine protease cruzain. Bioorg. Med. Chem. Lett. 11, 2759-2762.
65. Salmon, D., do Aido-Machado, R., Diehl, A., Leidert, M., Schmetzer, O., de A Lima, A.P., Scharfstein, J., Oschkinat, H., and Pires, J.R. (2006). Solution structure and backbone dynamics of the Trypanosoma cruzi cysteine protease inhibitor chagasin. J. Mol. Biol. 357, 1511-1521.
66. Sansonetti, P.J. (2006). The innate signaling of dangers and the dangers of innate signaling. Nat. Immunol. 7, 1237-1242.
67. Santos, C.C., Santanna, C., Terres, A., Cunha-e-Silva, N.L., Scharfstein, J., and Lima, A.P. (2005). Chagasin, the endogenous cysteine-protease inhibitor of Trypanosoma cruzi, modulates parasite differentiation and invasion of mammalian cells. J. Cell Sci. 118, 901-915.
68. Scharfstein, J. (2002). Activation of bradykinin receptors by Trypanosoma cruzi: a role for cruzipain in microvascular pathology. In: Molecular Mechanisms in the Pathogenesis of Chagas' Disease, J. Kelly, ed. (Austin, USA: Landes Biosciences), pp. 1-27.
69. Scharfstein, J., Rodrigues, M.M., Alves, C.A., de Souza, W., Previato, J.O., and Mendonça-Previato, L. (1983). Trypanosoma cruzi: description of a highly purified surface antigen defined by human antibodies. J. Immunol. 131, 972-976.
70. Scharfstein, J., Schechter, M., Senna, M., Peralta, J.M., Mendonça-Previato, L., and Miles, M.A. (1986). Trypanosoma cruzi: characterization and isolation of a 57/51 000 m.w. surface glycoprotein (GP57/51) expressed by epimastigotes and bloodstream trypomastigotes. J. Immunol. 137, 1336-1341.
71. Scharfstein, J., Abrahamson, M., de Souza, C.B., Barral, A., and Silva, I.V. (1995). Antigenicity of cystatin-binding proteins from parasitic protozoan. Detection by a proteinase inhibitor based capture immunoassay (PINC-ELISA). J. Immunol. Methods 182, 63-72.
72. 2 receptors. J. Exp. Med. 192, 1289-1300.
73. Scharfstein, J., Schmitz, V., Svensjö, E., Granato, A., and Monteiro, A.C. (2007). Kininogens coordinate adaptive immunity through the proteolytic release of bradykinin, an endogenous danger signal driving dendritic cell maturation. Scand. J. Immunol. 66, 128-136.
74. Scholzen, T.E., Ständer, S., Riemann, H., Brzoska, T., and Luger, T.A. (2003). Modulation of cutaneous inflammation by angiotensin-converting enzyme. J. Immunol. 170, 3866-3873.
75. Shen, X.Z., Xiao, H.D., Li, P., Lin, C.X., Fuchs, S., and Bernstein, K.E. (2008). Tissue specific expression of angiotensin converting enzyme: a new way to study an old friend. Int. Immunopharmacol. 8, 171-176.
76. Shortman, K. and Naik, S.H. (2007). Steady-state and inflammatory dendritic-cell development. Nat. Rev. Immunol. 7, 19-30.
77. Silva, J.S., Vespa, G.N., Cardoso, M.A., Aliberti, J.C., and Cunha, F.Q. (1995). Tumor necrosis factor α mediates resistance to Trypanosoma cruzi infection in mice by inducing nitric oxide production in infected γ interferon-activated macrophages. Infect. Immun. 63, 4862-4867.
78. Skidgel, R.A. and Erdös, E.G. (2004). Angiotensin converting enzyme (ACE) and neprilysin hydrolyze neuropeptides: a brief history, the beginning and follow-ups to early studies. Peptides 25, 521-525.
79. Steinman, R.M. and Nussenzweig, M.C. (2002). Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl. Acad. Sci. USA 99, 351-358.
80. Stoka, V., Nycander, M., Lenarcic, B., Labriola, C., Cazzulo, J.J., Björk, I., and Turk, V. (1995). Inhibition of cruzipain, the major cysteine proteinase of the protozoan parasite, Trypanosoma cruzi, by proteinase inhibitors of the cystatin superfamily. FEBS Lett. 370, 101-104.
81. + T cells. Immunity 28, 425-435.
82. Svensjö, E., Batista, P.R., Brodskyn, C.I., Silva, R., Lima, A.P., Schmitz, V., Saraiva, E., Pesquero, J.B., Mori, M.A., Müller-Esterl, W., et al. (2006). Interplay between parasite cysteine proteases and the host kinin system modulates microvascular leakage and macrophage infection by promastigotes of the Leishmania donovani complex. Microbes Infect. 8, 206-220.
83. Tardieux, I., Webster, P., Ravesloot, J., Boron, W., Lunn, J.A., Heuser, J.E., and Andrews, N.W. (1992). Lysosome recruitment and fusion are early events required for trypanosome invasion of mammalian cells. Cell 71, 1117-1130.
84. Tarleton, R.L. (2001). Parasite persistence in the aetiology of Chagas disease. Int. J. Parasitol. 31, 550-554.
85. Tarleton, R.L., Grusby, M.J., Postan, M., and Glimcher, L.H. (1996). Trypanosoma cruzi infection in MHC-deficient mice: further evidence for the role of both class I- and class II-restricted T cells in immune resistance and disease. Int. Immunol. 8, 13-22.
86. Todorov, A.G., Andrade, D., Pesquero, J.B., Araujo Rde, C., Bader, M., Stewart, J., Gera, L., Müller-Esterl, W., Morandi, V., Goldenberg, R.C., et al. (2003). Trypanosoma cruzi induces edematogenic responses in mice and invades cardiomyocytes and endothelial cells in vitro by activating distinct kinin receptor (B1/B2) subtypes. FASEB J. 17, 73-75.
87. + T cells leading to immunodominance. J. Immunol. 180, 1737-1748.
88. Varma, R., Campi, G., Yokosuka, T., Saito, T., and Dustin, M.L. (2006). T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster. Immunity 25, 117-127.
89. Wang, S.X., Pandey, K.C., Scharfstein, J., Whisstock, J., Huang, R.K., Jacobelli, J., Fletterick, R.J., Rosenthal, P.J., Abrahamson, M., Brinen, L.S., et al. (2007). The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family. Structure 15, 535-543.
90. Woolsey, A.M., Sunwoo, L., Petersen, C.A., Brachmann, S.M., Cantley, L.C., and Burleigh, B.A. (2003). Novel PI 3-kinase-dependent mechanisms of trypanosome invasion and vacuole maturation. J. Cell Sci. 116, 3611-3622.