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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/27713

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network_name_str CONICET Digital (CONICET)
spelling 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
reponame_str CONICET Digital (CONICET)
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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