Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease
- Autores
- Chowdhury, Imran H; Koo, Sue-jie; Gupta, Shivali; Liang, Lisa Yi; Bahar, Bojlul; Silla, Laura; Nuñez Burgos, Julio; Barrientos, Natalia; Zago, María Paola; Garg, Nisha Jain
- Año de publicación
- 2016
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host?s signature of the inflammatory/oxidative state and provide information regarding the progression of clinical disease. Methods: MPs were harvested from supernatants of human peripheral blood mononuclear cells in vitro incubated with Tc (control: LPS treated), plasma of seropositive humans with a clinically asymptomatic (CA) or symptomatic (CS) disease state (vs. normal/healthy [NH] controls), and plasma of mice immunized with a protective vaccine before challenge infection (control: unvaccinated/infected). Macrophages (mφs) were incubated with MPs, and we probed the gene expression profile using the inflammatory signaling cascade and cytokine/chemokine arrays, phenotypic markers of mφ activation by flow cytometry, cytokine profile by means of an ELISA and Bioplex assay, and oxidative/nitrosative stress and mitotoxicity by means of colorimetric and fluorometric assays. Results: Tc - and LPS-induced MPs stimulated proliferation, inflammatory gene expression profile, and nitric oxide (∙ NO) release in human THP-1 mφs. LPS-MPs were more immunostimulatory than Tc -MPs. Endothelial cells, T lymphocytes, and mφs were the major source of MPs shed in the plasma of chagasic humans and experimentally infected mice. The CS and CA (vs. NH) MPs elicited >2-fold increase in NO and mitochondrial oxidative stress in THP-1 mφs; however, CS(vs. CA) MPs elicited a more pronounced and disease-statespecific inflammatory gene expression profile (IKBKB, NR3C1, and TIRAP vs. CCR4, EGR2, and CCL3), cytokine release (IL-2 + IFN-γ > GCSF), and surface markers of mφ activation (CD14 and CD16). The circulatory MPs of nonvaccinated/infected mice induced 7.5-fold and 40% increases in ∙ NO and IFN-γ production, respectively, while these responses were abolished when RAW264.7 mφs were incubated with circulatory MPs of vaccinated/infected mice. Conclusion: Circulating MPs reflect in vivo levels of an oxidative, nitrosative, and inflammatory state, and have potential utility in evaluating disease severity and the efficacy of vaccines and drug therapies against CCM.
Fil: Chowdhury, Imran H. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos
Fil: Koo, Sue-jie. University of Texas; Estados Unidos
Fil: Gupta, Shivali. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos
Fil: Liang, Lisa Yi. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos
Fil: Bahar, Bojlul. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos
Fil: Silla, Laura. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos
Fil: Nuñez Burgos, Julio. No especifíca;
Fil: Barrientos, Natalia. No especifíca;
Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina
Fil: Garg, Nisha Jain . University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos - Materia
-
Chagasic Cardiomyopathy
Microparticles
Macrophage Activation - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/27713
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oai:ri.conicet.gov.ar:11336/27713 |
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Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas DiseaseChowdhury, Imran HKoo, Sue-jieGupta, ShivaliLiang, Lisa YiBahar, BojlulSilla, LauraNuñez Burgos, JulioBarrientos, NataliaZago, María PaolaGarg, Nisha Jain Chagasic CardiomyopathyMicroparticlesMacrophage Activationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host?s signature of the inflammatory/oxidative state and provide information regarding the progression of clinical disease. Methods: MPs were harvested from supernatants of human peripheral blood mononuclear cells in vitro incubated with Tc (control: LPS treated), plasma of seropositive humans with a clinically asymptomatic (CA) or symptomatic (CS) disease state (vs. normal/healthy [NH] controls), and plasma of mice immunized with a protective vaccine before challenge infection (control: unvaccinated/infected). Macrophages (mφs) were incubated with MPs, and we probed the gene expression profile using the inflammatory signaling cascade and cytokine/chemokine arrays, phenotypic markers of mφ activation by flow cytometry, cytokine profile by means of an ELISA and Bioplex assay, and oxidative/nitrosative stress and mitotoxicity by means of colorimetric and fluorometric assays. Results: Tc - and LPS-induced MPs stimulated proliferation, inflammatory gene expression profile, and nitric oxide (∙ NO) release in human THP-1 mφs. LPS-MPs were more immunostimulatory than Tc -MPs. Endothelial cells, T lymphocytes, and mφs were the major source of MPs shed in the plasma of chagasic humans and experimentally infected mice. The CS and CA (vs. NH) MPs elicited >2-fold increase in NO and mitochondrial oxidative stress in THP-1 mφs; however, CS(vs. CA) MPs elicited a more pronounced and disease-statespecific inflammatory gene expression profile (IKBKB, NR3C1, and TIRAP vs. CCR4, EGR2, and CCL3), cytokine release (IL-2 + IFN-γ > GCSF), and surface markers of mφ activation (CD14 and CD16). The circulatory MPs of nonvaccinated/infected mice induced 7.5-fold and 40% increases in ∙ NO and IFN-γ production, respectively, while these responses were abolished when RAW264.7 mφs were incubated with circulatory MPs of vaccinated/infected mice. Conclusion: Circulating MPs reflect in vivo levels of an oxidative, nitrosative, and inflammatory state, and have potential utility in evaluating disease severity and the efficacy of vaccines and drug therapies against CCM.Fil: Chowdhury, Imran H. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados UnidosFil: Koo, Sue-jie. University of Texas; Estados UnidosFil: Gupta, Shivali. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados UnidosFil: Liang, Lisa Yi. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados UnidosFil: Bahar, Bojlul. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados UnidosFil: Silla, Laura. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados UnidosFil: Nuñez Burgos, Julio. No especifíca;Fil: Barrientos, Natalia. No especifíca;Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Garg, Nisha Jain . University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados UnidosKarger2016-12-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/27713Chowdhury, Imran H; Koo, Sue-jie; Gupta, Shivali; Liang, Lisa Yi; Bahar, Bojlul; et al.; Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease; Karger; Journal of Innate Immunity; 9; 2; 1-12-2016; 1-141662-811XCONICET DigitalCONICETenginfo:eu-repo/semantics/reference/url/https://www.karger.com/Article/Abstract/451055info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/Abstract/451055info:eu-repo/semantics/altIdentifier/doi/10.1159/000451055info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:32:45Zoai:ri.conicet.gov.ar:11336/27713instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:32:46.23CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease |
title |
Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease |
spellingShingle |
Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease Chowdhury, Imran H Chagasic Cardiomyopathy Microparticles Macrophage Activation |
title_short |
Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease |
title_full |
Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease |
title_fullStr |
Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease |
title_full_unstemmed |
Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease |
title_sort |
Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease |
dc.creator.none.fl_str_mv |
Chowdhury, Imran H Koo, Sue-jie Gupta, Shivali Liang, Lisa Yi Bahar, Bojlul Silla, Laura Nuñez Burgos, Julio Barrientos, Natalia Zago, María Paola Garg, Nisha Jain |
author |
Chowdhury, Imran H |
author_facet |
Chowdhury, Imran H Koo, Sue-jie Gupta, Shivali Liang, Lisa Yi Bahar, Bojlul Silla, Laura Nuñez Burgos, Julio Barrientos, Natalia Zago, María Paola Garg, Nisha Jain |
author_role |
author |
author2 |
Koo, Sue-jie Gupta, Shivali Liang, Lisa Yi Bahar, Bojlul Silla, Laura Nuñez Burgos, Julio Barrientos, Natalia Zago, María Paola Garg, Nisha Jain |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
Chagasic Cardiomyopathy Microparticles Macrophage Activation |
topic |
Chagasic Cardiomyopathy Microparticles Macrophage Activation |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host?s signature of the inflammatory/oxidative state and provide information regarding the progression of clinical disease. Methods: MPs were harvested from supernatants of human peripheral blood mononuclear cells in vitro incubated with Tc (control: LPS treated), plasma of seropositive humans with a clinically asymptomatic (CA) or symptomatic (CS) disease state (vs. normal/healthy [NH] controls), and plasma of mice immunized with a protective vaccine before challenge infection (control: unvaccinated/infected). Macrophages (mφs) were incubated with MPs, and we probed the gene expression profile using the inflammatory signaling cascade and cytokine/chemokine arrays, phenotypic markers of mφ activation by flow cytometry, cytokine profile by means of an ELISA and Bioplex assay, and oxidative/nitrosative stress and mitotoxicity by means of colorimetric and fluorometric assays. Results: Tc - and LPS-induced MPs stimulated proliferation, inflammatory gene expression profile, and nitric oxide (∙ NO) release in human THP-1 mφs. LPS-MPs were more immunostimulatory than Tc -MPs. Endothelial cells, T lymphocytes, and mφs were the major source of MPs shed in the plasma of chagasic humans and experimentally infected mice. The CS and CA (vs. NH) MPs elicited >2-fold increase in NO and mitochondrial oxidative stress in THP-1 mφs; however, CS(vs. CA) MPs elicited a more pronounced and disease-statespecific inflammatory gene expression profile (IKBKB, NR3C1, and TIRAP vs. CCR4, EGR2, and CCL3), cytokine release (IL-2 + IFN-γ > GCSF), and surface markers of mφ activation (CD14 and CD16). The circulatory MPs of nonvaccinated/infected mice induced 7.5-fold and 40% increases in ∙ NO and IFN-γ production, respectively, while these responses were abolished when RAW264.7 mφs were incubated with circulatory MPs of vaccinated/infected mice. Conclusion: Circulating MPs reflect in vivo levels of an oxidative, nitrosative, and inflammatory state, and have potential utility in evaluating disease severity and the efficacy of vaccines and drug therapies against CCM. Fil: Chowdhury, Imran H. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos Fil: Koo, Sue-jie. University of Texas; Estados Unidos Fil: Gupta, Shivali. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos Fil: Liang, Lisa Yi. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos Fil: Bahar, Bojlul. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos Fil: Silla, Laura. University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos Fil: Nuñez Burgos, Julio. No especifíca; Fil: Barrientos, Natalia. No especifíca; Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina Fil: Garg, Nisha Jain . University Of Texas Medical Branch. Institute for Human Infections and Immunity; Estados Unidos |
description |
Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host?s signature of the inflammatory/oxidative state and provide information regarding the progression of clinical disease. Methods: MPs were harvested from supernatants of human peripheral blood mononuclear cells in vitro incubated with Tc (control: LPS treated), plasma of seropositive humans with a clinically asymptomatic (CA) or symptomatic (CS) disease state (vs. normal/healthy [NH] controls), and plasma of mice immunized with a protective vaccine before challenge infection (control: unvaccinated/infected). Macrophages (mφs) were incubated with MPs, and we probed the gene expression profile using the inflammatory signaling cascade and cytokine/chemokine arrays, phenotypic markers of mφ activation by flow cytometry, cytokine profile by means of an ELISA and Bioplex assay, and oxidative/nitrosative stress and mitotoxicity by means of colorimetric and fluorometric assays. Results: Tc - and LPS-induced MPs stimulated proliferation, inflammatory gene expression profile, and nitric oxide (∙ NO) release in human THP-1 mφs. LPS-MPs were more immunostimulatory than Tc -MPs. Endothelial cells, T lymphocytes, and mφs were the major source of MPs shed in the plasma of chagasic humans and experimentally infected mice. The CS and CA (vs. NH) MPs elicited >2-fold increase in NO and mitochondrial oxidative stress in THP-1 mφs; however, CS(vs. CA) MPs elicited a more pronounced and disease-statespecific inflammatory gene expression profile (IKBKB, NR3C1, and TIRAP vs. CCR4, EGR2, and CCL3), cytokine release (IL-2 + IFN-γ > GCSF), and surface markers of mφ activation (CD14 and CD16). The circulatory MPs of nonvaccinated/infected mice induced 7.5-fold and 40% increases in ∙ NO and IFN-γ production, respectively, while these responses were abolished when RAW264.7 mφs were incubated with circulatory MPs of vaccinated/infected mice. Conclusion: Circulating MPs reflect in vivo levels of an oxidative, nitrosative, and inflammatory state, and have potential utility in evaluating disease severity and the efficacy of vaccines and drug therapies against CCM. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-12-01 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/27713 Chowdhury, Imran H; Koo, Sue-jie; Gupta, Shivali; Liang, Lisa Yi; Bahar, Bojlul; et al.; Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease; Karger; Journal of Innate Immunity; 9; 2; 1-12-2016; 1-14 1662-811X CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/27713 |
identifier_str_mv |
Chowdhury, Imran H; Koo, Sue-jie; Gupta, Shivali; Liang, Lisa Yi; Bahar, Bojlul; et al.; Gene Expression Profiling and Functional Characterization of Macrophages in Response to Circulatory Microparticles Produced during Trypanosoma cruzi Infection and Chagas Disease; Karger; Journal of Innate Immunity; 9; 2; 1-12-2016; 1-14 1662-811X CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/reference/url/https://www.karger.com/Article/Abstract/451055 info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/Abstract/451055 info:eu-repo/semantics/altIdentifier/doi/10.1159/000451055 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Karger |
publisher.none.fl_str_mv |
Karger |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |