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.
Descargas
Los datos de descargas todavía no están disponibles.
Referencias bibliográficas
1. Revy P, Sosperda M, Barbour B, Trautmann A. Functional antigen-independent synapses formed between T cells and dendritic cells. Nat Immunol 2001;2:925-31.
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.
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. Biomed. [Internet]. 1 de enero de 2007 [citado 4 de abril de 2025];27(1esp):18-27. Disponible en: https://revistabiomedicaorg.biteca.online/index.php/biomedica/article/view/245
Algunos artículos similares:
- Iveth J. González, Las metacaspasas y su rol en la vida y muerte de los parásitos protozoarios humanos , Biomédica: Vol. 29 Núm. 3 (2009)
- Andrea Arévalo, Julio César Carranza, Felipe Guhl, Jairo A. Clavijo, Gustavo Adolfo Vallejo, Comparación de los patrones de alimentación y defecación de Rhodnius colombiensis y Rhodnius prolixus (Hemiptera, Reduviidae, Triatominae) en condiciones de laboratorio , Biomédica: Vol. 27 Núm. 1esp (2007): Enfermedad de Chagas
- Gustavo Adolfo Vallejo, Felipe Guhl, Julio César Carranza, Omar Triana, Gerardo Pérez, Paola Andrea Ortiz, Dairo Humberto Marín, Lina Marcela Villa, Jazmín Suárez, Isaura Pilar Sánchez, Ximena Pulido, Ingrid Bibiana Rodríguez, Leyder Elena Lozano, Daniel Alfonso Urrea, Fredy Arvey Rivera, César Cuba-Cuba, Jairo Alfonso Clavijo, Interacción tripanosoma-vector-vertebrado y su relación con la sistemática y la epidemiología de la tripanosomiasis americana , Biomédica: Vol. 27 Núm. 1esp (2007): Enfermedad de Chagas
- Myriam C. López, Sofía Duque, Luis C. Orozco, Diana Camargo, Luis E. Gualdrón, Elvia Cáceres, Margarita Ronderos, Maritza Rey, Augusto Corredor, Inmunodiagnóstico de la infección chagásica por ELlSA , Biomédica: Vol. 19 Núm. 2 (1999)
- Luis C. Orozco, Diana Camargo, Myriam C. López, Sofía Duque, Luis E. Gualdrón, Elvia Cáceres, Margarita Ronderos, Maritza Rey, Augusto Corredor, Inmunodiagnóstico de la infección en humanos por Trypanosoma cruzi mediante ELISA utilizando sangre recolectada en papel de filtro , Biomédica: Vol. 19 Núm. 2 (1999)
- Claudia Urueña, Paola Santander, Hugo Díez, Marleny Montilla, Ignacio Zarante, María del Carmen Thomas, Manuel Carlos López, Concepción Puerta, Localización cromosómica de los genes KMP-11 en cepas KP1(+) y KP1 (-) de Trypanosoma rangeli. , Biomédica: Vol. 24 Núm. 2 (2004)
Sección
Artículos originales
| Estadísticas de artículo | |
|---|---|
| Vistas de resúmenes | |
| Vistas de PDF | |
| Descargas de PDF | |
| Vistas de HTML | |
| Otras vistas | |
