Expresión de marcadores en células dendríticas de pacientes chagásicos crónicos estimuladas con la proteína KMP-11 y el péptido K1 de Trypanosoma cruzi
Palabras clave:
enfermedad de Chagas, interleucina-12, Trypanosoma cruzi
Resumen
Introducción. La proteína de membrana 11 de kinetoplástidos, KMP-11, de Trypanosoma cruzi induce inmunidad humoral y celular en ratones capaz de conferir protección frente al reto con el parásito.Objetivo. Determinar la expresión de marcadores de maduración en las células dendríticas de pacientes chagásicos crónicos e individuos sanos, estimuladas con la proteína KMP-11 y su péptido amino terminal K1.
Materiales y métodos. Monocitos de siete pacientes chagásicos y siete individuos sanos fueron diferenciados a células dendríticas y estimulados con la proteína KMP-11 y el péptido K1, determinándose por citometría de flujo y tras 7 días de cultivo, la expresión de los marcadores de superficie CD83, CD86 y HLA-DR y la producción de citocinas.
Resultados. La proteína KMP-11 y el péptido K1 no indujeron la expresión del marcador de maduración CD83 en las células dendríticas de pacientes y controles. La exposición de células dendríticas de pacientes chagásicos de forma simultánea al péptido K1 y LPS mostró una disminución de la expresión de CD86 y CD83 con relación a la estimulación con LPS sólo, a diferencia de las células de controles sanos. También se evidenció una disminución en la producción de interleucina-12 en las células dendríticas de pacientes en relación a las de los controles.
Conclusiones. La proteína KMP-11 no tiene un efecto significativo sobre la maduración de las células dendríticas, pero su péptido K1 en presencia de LPS induce una disminución en la expresión de CD86 y CD83 y en la producción de la interleucina-12 que podría modular la respuesta inmune in vivo y en particular la estimulación de los linfocitos T.
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Referencias bibliográficas
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Trypanosoma cruzi. Parasite Immunol 2006;28:101-5.
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thiazolidine linkages. J Pept Res 2001;58:307-16.
15. Thomas MC, Longobardo MV, Carmelo E, Maranon C, Planelles L, Patarroyo ME, et al. Mapping of the antigenic determinants of the T. cruzi kinetoplastid membrane protein-11. Identification of a linear epitope specifically recognized by human Chagasic sera. Clin Exp Immunol 2001;123:465-71.
16. Cuéllar A, Fonseca A, Gómez A. Efecto del lipopolisacárido en cultivos de células dendríticas humanas y su inhibición por la polimixina B. Biomédica 2004;24:413-22.
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22. Smits HH, Engering A, van der Kleij D, De Jong EC, Schipper K, van Capel TM, et al. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol 2005;115:1260-7.
23. Auffermann-Gretzinger S, Keeffe EB, Levy S. Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection. Blood 2001;97:3171-6.
24. Brodskyn C, Patricio J, Oliveira R, Lobo L, Arnholdt A, Mendonca-Previato L, et al. Glycoinositolphospholipids from Trypanosoma cruzi interfere with macrophages and dendritic cell responses. Infect Immun 2002;70:3736-43.
25.Ouaissi A, Guilvard E, Delneste Y, Caron G, Magistrelli G, Herbault N, et al. The Trypanosoma cruzi Tc52-released protein induces human dendritic cell maturation, signals via toll-like receptor 2, and confers protection against lethal infection. J Immunol 2002;168:6366-74.
26. Jardim A, Hanson S, Ullman B, McCubbin WD, Kay CM, Olafson RW. Cloning and structure-function analysis of the Leishmania donovanni kinetoplastid membrane protein-11. Biochem J 1995;305:315-20.
27. Thomas MC, García-Pérez JL, Alonso C, López MC. Molecular characterization of KMP-11 from Trypanosoma cruzi: a cytoskeleton-associated protein regulated at the translational level. DNA Cell Biol
2000;19:47-57.
28. Stebeck CE, Baron GS, Beecroft RP, Pearson TW. Molecular characterization of the kinetoplastid membrane protein-11 from African trypanosomes. Mol Biochem Parasitol 1996;81:81-8.
29. Diez H, López MC, Thomas MC, Guzman F, Rosas F, Velasco V, et al. Respuesta inmune al péptido K1 en pacientes infectados con Trypanosoma cruzi. Parasitol Latin 2005;60:208.
30. Hoft DF, Eickhoff CS. Type 1 immunity provides optimal protection against both mucosal and systemic Trypanosoma cruzi challenges. Infect Immun 2002;70:6715-25.
31. Kumar S, Tarleton RL. Antigen-specific Th1 but not Th2 cells provide protection from lethal Trypanosoma cruzi infection in mice. J Immunol 2001;166:4596-603.
32. Planelles L, Thomas MC, Marañon C, Morell M, López MC. Differential CD86 and CD40 co-stimulatory molecules and cytokine expression pattern induced by Trypanosoma cruzi in APCs from resistant or
susceptible mice. Clin Exp Immunol 2003;131:41-7.
33. Planelles L, Thomas M, Pulgar M, Marañon C, Grabbe S, López MC. Trypanosoma cruzi heat-shock protein-70 kDa, alone or fused to the parasite KMP-11 antigen, induces functional maturation of murine
dendritic cells. Immunol Cell Biol 2002;80:241-7.
34. Braun MC, Wang JM, Lahey E, Rabin RL, Kelsall BL. Activation of the formyl peptide receptor by the HIV-derived peptide T-20 suppresses interleukin-12 p70 production by human monocytes. Blood 2001;97:3531-6.
35. Kang HK, Lee HY, Kim MK, Park KS, Park YM, Kwak JY, et al. The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met inhibits human monocyte-derived dendritic cell maturation via formyl peptide receptor and formyl peptide receptor-like 2. J Immunol 2005;175:685-92.
36. Betten A, Bylund J, Cristophe T, Boulay F, Romero A, Hellstrand K, et al. A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis. J Clin Invest 2001;108:1221-8.
37. Hartt JK, Liang T, Sahagun-Ruiz A, Wang JM, Gao JL, Murphy PM. The HIV-1 cell entry inhibitor T-20 potently chemoattracts neutrophils by specifically activating the N-formylpeptide receptor. Biochem Biophys Res Commun 2000;272:699-704.
38. Bylund J, Christophe T, Boulay F, Nystrom T, Karlsson A, Dahlgren C. Proinflammatory activity of a cecropin-like antibacterial peptide from Helicobacter pylori. Antimicrob Agents Chemother 2001;45:1700-4.
39. Mandal P, Novotny M, Hamilton TA. Lipopolysaccharide induces formyl peptide receptor 1 gene expression in macrophages and neutrophils via transcriptional and posttranscriptional mechanisms. J
Immunol 2005;175:6085-91.
2. Russo V, Tanzarella S, Dalerba P, Rigatti D, Rovere P, Villa A, et al. Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class I restricted T cell response. Proc Natl Acad Sci USA 2000;97:2185-90.
3. Lanzavecchia A, Sallusto F. The instructive role of dendritic cells on T cell responses: lineages, plasticity and kinetics. Curr Opin Immunol 2001;13:291-8.
4. World Health Organization. Control of Chagas disease. Second report of the WHO Expert Committee, Technical Report 2002, Series 905. Geneva: WHO; 2002. p.39-40.
5. Moncayo A. Chagas disease: current epidemiological trends after the interruption of vectorial and transfusional transmission in the Southern Cone countries. Mem Inst Oswaldo Cruz 2003;98:577-91.
6. Tanowitz HB, Kirchhoff LV, Simon D, Morris SA, Weiss LM, Wittner M. Chagas' disease. Clin Microbiol Rev 1992;5:400-19.
7. Van Overtvelt L, Vanderheyde N, Verhasselt V, Ismaili J, De Vos L, Goldman M, et al. Trypanosoma cruzi infects human dendritic cells and prevents their maturation: inhibition of cytokines, HLA-DR, and costimulatory molecules. Infect Immun 1999;67:4033-40.
8. Van Overtvelt L, Andrieu M, Verhasselt V, Connan F, Choppin J, Vercruysse V, et al. Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8(+) T lymphocytes. Int Immunol 2002;14:1135-44.
9. Marañon C, Thomas MC, Planelles L, Lopez MC. The immunization of A2/K(b) transgenic mice with the KMP-11-HSP70 fusion protein induces CTL response against human cells expressing the T. cruzi KMP-11 antigen: Identification of A2-restricted epitopes. Mol Immunol 2001;38:279-87.
10. Rodrigues MM, Ribeirao M, Pereira-Chioccola V, Renia L, Costa F. Predominance of CD4 Th1 and CD8 Tc1 cells revealed by characterization of the cellular immune response generated by immunization
with a DNA vaccine containing a Trypanosoma cruzi gene. Infect Immun 1999;67:3855-63.
11. Villalta F, Lima MF, Howard SA, Zhou L, Ruíz-Ruano A. Purification of a Trypanosoma cruzi trypomastigote 60-Kilodalton surface glycoprotein that primes and activates murine lymphocytes. Infect Immun 1992;60:3025-32.
12. Planelles L, Thomas MC, Alonso C, Lopez MC. DNA immunization with Trypanosoma cruzi HSP70 fused to the KMP-11 protein elicits a cytotoxic and humoral immune response against the antigen and leads to protection. Infect Immun 2001;69:6558-63.
13. Diez H, López MC, Thomas MC, Guzman F, Rosas F, Velazco V. et al. Evaluation of IFNg production by CD8+ T lymphocytes in response to the K1 peptide from KMP-11 protein in patients infected with
Trypanosoma cruzi. Parasite Immunol 2006;28:101-5.
14. Chaves F, Calvo JC, Carvajal C, Rivera Z, Ramirez L, Pinto M, et al. Synthesis, isolation and characterization of Plasmodium falciparum antigenic tetrabranched peptide dendrimers obtained by
thiazolidine linkages. J Pept Res 2001;58:307-16.
15. Thomas MC, Longobardo MV, Carmelo E, Maranon C, Planelles L, Patarroyo ME, et al. Mapping of the antigenic determinants of the T. cruzi kinetoplastid membrane protein-11. Identification of a linear epitope specifically recognized by human Chagasic sera. Clin Exp Immunol 2001;123:465-71.
16. Cuéllar A, Fonseca A, Gómez A. Efecto del lipopolisacárido en cultivos de células dendríticas humanas y su inhibición por la polimixina B. Biomédica 2004;24:413-22.
17. Modlin RL, Brightbill HD, Godowski PJ. The toll of innate immunity on microbial pathogens. N Engl J Med 1999;340:1834-5.
18. Lanzavecchia A, Sallusto F. Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells. Science 2000;290:92-7.
19. Moser M, Murphy KM. Dendritic cell regulation of TH1- TH2 development. Nat Immunol 2000;1:199-205.
20. Pearce EJ, Kane CM, Sun J. Regulation of dendritic cell function by pathogen-derived molecules plays a key role in dictating the outcome of the adaptive immune response. Chem Immunol Allergy 2006;90:82-90.
21. Lutz MB, Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol 2002;23:445-9.
22. Smits HH, Engering A, van der Kleij D, De Jong EC, Schipper K, van Capel TM, et al. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol 2005;115:1260-7.
23. Auffermann-Gretzinger S, Keeffe EB, Levy S. Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection. Blood 2001;97:3171-6.
24. Brodskyn C, Patricio J, Oliveira R, Lobo L, Arnholdt A, Mendonca-Previato L, et al. Glycoinositolphospholipids from Trypanosoma cruzi interfere with macrophages and dendritic cell responses. Infect Immun 2002;70:3736-43.
25.Ouaissi A, Guilvard E, Delneste Y, Caron G, Magistrelli G, Herbault N, et al. The Trypanosoma cruzi Tc52-released protein induces human dendritic cell maturation, signals via toll-like receptor 2, and confers protection against lethal infection. J Immunol 2002;168:6366-74.
26. Jardim A, Hanson S, Ullman B, McCubbin WD, Kay CM, Olafson RW. Cloning and structure-function analysis of the Leishmania donovanni kinetoplastid membrane protein-11. Biochem J 1995;305:315-20.
27. Thomas MC, García-Pérez JL, Alonso C, López MC. Molecular characterization of KMP-11 from Trypanosoma cruzi: a cytoskeleton-associated protein regulated at the translational level. DNA Cell Biol
2000;19:47-57.
28. Stebeck CE, Baron GS, Beecroft RP, Pearson TW. Molecular characterization of the kinetoplastid membrane protein-11 from African trypanosomes. Mol Biochem Parasitol 1996;81:81-8.
29. Diez H, López MC, Thomas MC, Guzman F, Rosas F, Velasco V, et al. Respuesta inmune al péptido K1 en pacientes infectados con Trypanosoma cruzi. Parasitol Latin 2005;60:208.
30. Hoft DF, Eickhoff CS. Type 1 immunity provides optimal protection against both mucosal and systemic Trypanosoma cruzi challenges. Infect Immun 2002;70:6715-25.
31. Kumar S, Tarleton RL. Antigen-specific Th1 but not Th2 cells provide protection from lethal Trypanosoma cruzi infection in mice. J Immunol 2001;166:4596-603.
32. Planelles L, Thomas MC, Marañon C, Morell M, López MC. Differential CD86 and CD40 co-stimulatory molecules and cytokine expression pattern induced by Trypanosoma cruzi in APCs from resistant or
susceptible mice. Clin Exp Immunol 2003;131:41-7.
33. Planelles L, Thomas M, Pulgar M, Marañon C, Grabbe S, López MC. Trypanosoma cruzi heat-shock protein-70 kDa, alone or fused to the parasite KMP-11 antigen, induces functional maturation of murine
dendritic cells. Immunol Cell Biol 2002;80:241-7.
34. Braun MC, Wang JM, Lahey E, Rabin RL, Kelsall BL. Activation of the formyl peptide receptor by the HIV-derived peptide T-20 suppresses interleukin-12 p70 production by human monocytes. Blood 2001;97:3531-6.
35. Kang HK, Lee HY, Kim MK, Park KS, Park YM, Kwak JY, et al. The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met inhibits human monocyte-derived dendritic cell maturation via formyl peptide receptor and formyl peptide receptor-like 2. J Immunol 2005;175:685-92.
36. Betten A, Bylund J, Cristophe T, Boulay F, Romero A, Hellstrand K, et al. A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis. J Clin Invest 2001;108:1221-8.
37. Hartt JK, Liang T, Sahagun-Ruiz A, Wang JM, Gao JL, Murphy PM. The HIV-1 cell entry inhibitor T-20 potently chemoattracts neutrophils by specifically activating the N-formylpeptide receptor. Biochem Biophys Res Commun 2000;272:699-704.
38. Bylund J, Christophe T, Boulay F, Nystrom T, Karlsson A, Dahlgren C. Proinflammatory activity of a cecropin-like antibacterial peptide from Helicobacter pylori. Antimicrob Agents Chemother 2001;45:1700-4.
39. Mandal P, Novotny M, Hamilton TA. Lipopolysaccharide induces formyl peptide receptor 1 gene expression in macrophages and neutrophils via transcriptional and posttranscriptional mechanisms. J
Immunol 2005;175:6085-91.
Cómo citar
1.
Santander SP, Cuéllar A, Thomas M del C, Guzmán F, Gómez A, López MC, et al. Expresión de marcadores en células dendríticas de pacientes chagásicos crónicos estimuladas con la proteína KMP-11 y el péptido K1 de Trypanosoma cruzi. biomedica [Internet]. 1 de enero de 2007 [citado 19 de abril de 2024];27(1esp):18-27. Disponible en: https://revistabiomedica.org/index.php/biomedica/article/view/245
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