Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC

Autores
Pieralisi, Azul Victoria; Cevey, Ágata Carolina; Penas, Federico Nicolás; Prado, Nilda; Mori, Ana; Gili, Mónica; Mirkin, Gerardo Ariel Isidoro; Gagliardi, Juan; Goren, Nora Beatriz
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chronic Chagas disease cardiomyopathy (CCC) is the most important clinical manifestation of infection with Trypanosma cruzi (T. cruzi) due to its frequency and effects on morbidity and mortality. Peripheral blood mononuclear cells (PBMC) infiltrate the tissue and differentiate into inflammatory macrophages. Advances in pathophysiology show that myeloid cell subpopulations contribute to cardiac homeostasis, emerging as possible therapeutic targets. We previously demonstrated that fenofibrate, PPARα agonist, controls inflammation, prevents fibrosis and improves cardiac function in a murine infection model. In this work we investigated the spontaneous release of inflammatory cytokines and chemokines, changes in the frequencies of monocyte subsets, and fenofibrate effects on PBMC of seropositive patients with different clinical stages of Chagas disease. The results show that PBMC from Chagas disease patients display higher levels of IL-12, TGF-β, IL-6, MCP1, and CCR2 than cells from uninfected individuals (HI), irrespectively of the clinical stage, asymptomatic (Asy) or with Chagas heart disease (CHD). Fenofibrate reduces the levels of pro-inflammatory mediators and CCR2 in both Asy and CHD patients. We found that CHD patients display a significantly higher percentage of classical monocytes in comparison with Asy patients and HI. Besides, Asy patients have a significantly higher percentage of non-classical monocytes than CHD patients or HI. However, no difference in the intermediate monocyte subpopulation was found between groups. Moreover, monocytes from Asy or CHD patients exhibit different responses upon stimulation in vitro with T. cruzi lysates and fenofibrate treatment. Stimulation with T. cruzi significantly increases the percentage of classical monocytes in the Asy group whereas the percentage of intermediate monocytes decreases. Besides, there are no changes in their frequencies in CHD or HI. Notably, stimulation with T. cruzi did not modify the frequency of the non-classical monocytes subpopulation in any of the groups studied. Moreover, fenofibrate treatment of T. cruzi-stimulated cells, increased the frequency of the non-classical subpopulation in Asy patients. Interestingly, fenofibrate restores CCR2 levels but does not modify HLA-DR expression in any groups. In conclusion, our results emphasize a potential role for fenofibrate as a modulator of monocyte subpopulations towards an anti-inflammatory and healing profile in different stages of chronic Chagas disease.
Fil: Pieralisi, Azul Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Cevey, Ágata Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Penas, Federico Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Prado, Nilda. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; Argentina
Fil: Mori, Ana. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; Argentina
Fil: Gili, Mónica. Hospital Municipal de Rehabilitacion Respiratoria Maria Ferrer ; Gobierno de la Ciudad Autonoma de Buenos Aires;
Fil: Mirkin, Gerardo Ariel Isidoro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Gagliardi, Juan. Hospital Municipal de Rehabilitacion Respiratoria Maria Ferrer ; Gobierno de la Ciudad Autonoma de Buenos Aires;
Fil: Goren, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Materia
CHRONIC CHAGAS DISEASE
CYTOKINE
FENOFIBRATE
INFLAMMATION
MONOCYTE SUBSETS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/211236
Acceder
id CONICETDig_72e7944c97dccd9b8f913f4e968df0ea
oai_identifier_str oai:ri.conicet.gov.ar:11336/211236
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network_name_str CONICET Digital (CONICET)
spelling Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMCPieralisi, Azul VictoriaCevey, Ágata CarolinaPenas, Federico NicolásPrado, NildaMori, AnaGili, MónicaMirkin, Gerardo Ariel IsidoroGagliardi, JuanGoren, Nora BeatrizCHRONIC CHAGAS DISEASECYTOKINEFENOFIBRATEINFLAMMATIONMONOCYTE SUBSETShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Chronic Chagas disease cardiomyopathy (CCC) is the most important clinical manifestation of infection with Trypanosma cruzi (T. cruzi) due to its frequency and effects on morbidity and mortality. Peripheral blood mononuclear cells (PBMC) infiltrate the tissue and differentiate into inflammatory macrophages. Advances in pathophysiology show that myeloid cell subpopulations contribute to cardiac homeostasis, emerging as possible therapeutic targets. We previously demonstrated that fenofibrate, PPARα agonist, controls inflammation, prevents fibrosis and improves cardiac function in a murine infection model. In this work we investigated the spontaneous release of inflammatory cytokines and chemokines, changes in the frequencies of monocyte subsets, and fenofibrate effects on PBMC of seropositive patients with different clinical stages of Chagas disease. The results show that PBMC from Chagas disease patients display higher levels of IL-12, TGF-β, IL-6, MCP1, and CCR2 than cells from uninfected individuals (HI), irrespectively of the clinical stage, asymptomatic (Asy) or with Chagas heart disease (CHD). Fenofibrate reduces the levels of pro-inflammatory mediators and CCR2 in both Asy and CHD patients. We found that CHD patients display a significantly higher percentage of classical monocytes in comparison with Asy patients and HI. Besides, Asy patients have a significantly higher percentage of non-classical monocytes than CHD patients or HI. However, no difference in the intermediate monocyte subpopulation was found between groups. Moreover, monocytes from Asy or CHD patients exhibit different responses upon stimulation in vitro with T. cruzi lysates and fenofibrate treatment. Stimulation with T. cruzi significantly increases the percentage of classical monocytes in the Asy group whereas the percentage of intermediate monocytes decreases. Besides, there are no changes in their frequencies in CHD or HI. Notably, stimulation with T. cruzi did not modify the frequency of the non-classical monocytes subpopulation in any of the groups studied. Moreover, fenofibrate treatment of T. cruzi-stimulated cells, increased the frequency of the non-classical subpopulation in Asy patients. Interestingly, fenofibrate restores CCR2 levels but does not modify HLA-DR expression in any groups. In conclusion, our results emphasize a potential role for fenofibrate as a modulator of monocyte subpopulations towards an anti-inflammatory and healing profile in different stages of chronic Chagas disease.Fil: Pieralisi, Azul Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Cevey, Ágata Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Penas, Federico Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Prado, Nilda. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; ArgentinaFil: Mori, Ana. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; ArgentinaFil: Gili, Mónica. Hospital Municipal de Rehabilitacion Respiratoria Maria Ferrer ; Gobierno de la Ciudad Autonoma de Buenos Aires;Fil: Mirkin, Gerardo Ariel Isidoro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Gagliardi, Juan. Hospital Municipal de Rehabilitacion Respiratoria Maria Ferrer ; Gobierno de la Ciudad Autonoma de Buenos Aires;Fil: Goren, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFrontiers Media2022-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/211236Pieralisi, Azul Victoria; Cevey, Ágata Carolina; Penas, Federico Nicolás; Prado, Nilda; Mori, Ana; et al.; Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC; Frontiers Media; Frontiers in Cellular and Infection Microbiology; 11; 1-2022; 1-152235-2988CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fcimb.2021.785166/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fcimb.2021.785166info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:02:55Zoai:ri.conicet.gov.ar:11336/211236instacron: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:34982025-10-22 12:02:55.437CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC
title Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC
spellingShingle Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC
Pieralisi, Azul Victoria
CHRONIC CHAGAS DISEASE
CYTOKINE
FENOFIBRATE
INFLAMMATION
MONOCYTE SUBSETS
title_short Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC
title_full Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC
title_fullStr Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC
title_full_unstemmed Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC
title_sort Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC
dc.creator.none.fl_str_mv Pieralisi, Azul Victoria
Cevey, Ágata Carolina
Penas, Federico Nicolás
Prado, Nilda
Mori, Ana
Gili, Mónica
Mirkin, Gerardo Ariel Isidoro
Gagliardi, Juan
Goren, Nora Beatriz
author Pieralisi, Azul Victoria
author_facet Pieralisi, Azul Victoria
Cevey, Ágata Carolina
Penas, Federico Nicolás
Prado, Nilda
Mori, Ana
Gili, Mónica
Mirkin, Gerardo Ariel Isidoro
Gagliardi, Juan
Goren, Nora Beatriz
author_role author
author2 Cevey, Ágata Carolina
Penas, Federico Nicolás
Prado, Nilda
Mori, Ana
Gili, Mónica
Mirkin, Gerardo Ariel Isidoro
Gagliardi, Juan
Goren, Nora Beatriz
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CHRONIC CHAGAS DISEASE
CYTOKINE
FENOFIBRATE
INFLAMMATION
MONOCYTE SUBSETS
topic CHRONIC CHAGAS DISEASE
CYTOKINE
FENOFIBRATE
INFLAMMATION
MONOCYTE SUBSETS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Chronic Chagas disease cardiomyopathy (CCC) is the most important clinical manifestation of infection with Trypanosma cruzi (T. cruzi) due to its frequency and effects on morbidity and mortality. Peripheral blood mononuclear cells (PBMC) infiltrate the tissue and differentiate into inflammatory macrophages. Advances in pathophysiology show that myeloid cell subpopulations contribute to cardiac homeostasis, emerging as possible therapeutic targets. We previously demonstrated that fenofibrate, PPARα agonist, controls inflammation, prevents fibrosis and improves cardiac function in a murine infection model. In this work we investigated the spontaneous release of inflammatory cytokines and chemokines, changes in the frequencies of monocyte subsets, and fenofibrate effects on PBMC of seropositive patients with different clinical stages of Chagas disease. The results show that PBMC from Chagas disease patients display higher levels of IL-12, TGF-β, IL-6, MCP1, and CCR2 than cells from uninfected individuals (HI), irrespectively of the clinical stage, asymptomatic (Asy) or with Chagas heart disease (CHD). Fenofibrate reduces the levels of pro-inflammatory mediators and CCR2 in both Asy and CHD patients. We found that CHD patients display a significantly higher percentage of classical monocytes in comparison with Asy patients and HI. Besides, Asy patients have a significantly higher percentage of non-classical monocytes than CHD patients or HI. However, no difference in the intermediate monocyte subpopulation was found between groups. Moreover, monocytes from Asy or CHD patients exhibit different responses upon stimulation in vitro with T. cruzi lysates and fenofibrate treatment. Stimulation with T. cruzi significantly increases the percentage of classical monocytes in the Asy group whereas the percentage of intermediate monocytes decreases. Besides, there are no changes in their frequencies in CHD or HI. Notably, stimulation with T. cruzi did not modify the frequency of the non-classical monocytes subpopulation in any of the groups studied. Moreover, fenofibrate treatment of T. cruzi-stimulated cells, increased the frequency of the non-classical subpopulation in Asy patients. Interestingly, fenofibrate restores CCR2 levels but does not modify HLA-DR expression in any groups. In conclusion, our results emphasize a potential role for fenofibrate as a modulator of monocyte subpopulations towards an anti-inflammatory and healing profile in different stages of chronic Chagas disease.
Fil: Pieralisi, Azul Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Cevey, Ágata Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Penas, Federico Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Prado, Nilda. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; Argentina
Fil: Mori, Ana. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; Argentina
Fil: Gili, Mónica. Hospital Municipal de Rehabilitacion Respiratoria Maria Ferrer ; Gobierno de la Ciudad Autonoma de Buenos Aires;
Fil: Mirkin, Gerardo Ariel Isidoro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Gagliardi, Juan. Hospital Municipal de Rehabilitacion Respiratoria Maria Ferrer ; Gobierno de la Ciudad Autonoma de Buenos Aires;
Fil: Goren, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
description Chronic Chagas disease cardiomyopathy (CCC) is the most important clinical manifestation of infection with Trypanosma cruzi (T. cruzi) due to its frequency and effects on morbidity and mortality. Peripheral blood mononuclear cells (PBMC) infiltrate the tissue and differentiate into inflammatory macrophages. Advances in pathophysiology show that myeloid cell subpopulations contribute to cardiac homeostasis, emerging as possible therapeutic targets. We previously demonstrated that fenofibrate, PPARα agonist, controls inflammation, prevents fibrosis and improves cardiac function in a murine infection model. In this work we investigated the spontaneous release of inflammatory cytokines and chemokines, changes in the frequencies of monocyte subsets, and fenofibrate effects on PBMC of seropositive patients with different clinical stages of Chagas disease. The results show that PBMC from Chagas disease patients display higher levels of IL-12, TGF-β, IL-6, MCP1, and CCR2 than cells from uninfected individuals (HI), irrespectively of the clinical stage, asymptomatic (Asy) or with Chagas heart disease (CHD). Fenofibrate reduces the levels of pro-inflammatory mediators and CCR2 in both Asy and CHD patients. We found that CHD patients display a significantly higher percentage of classical monocytes in comparison with Asy patients and HI. Besides, Asy patients have a significantly higher percentage of non-classical monocytes than CHD patients or HI. However, no difference in the intermediate monocyte subpopulation was found between groups. Moreover, monocytes from Asy or CHD patients exhibit different responses upon stimulation in vitro with T. cruzi lysates and fenofibrate treatment. Stimulation with T. cruzi significantly increases the percentage of classical monocytes in the Asy group whereas the percentage of intermediate monocytes decreases. Besides, there are no changes in their frequencies in CHD or HI. Notably, stimulation with T. cruzi did not modify the frequency of the non-classical monocytes subpopulation in any of the groups studied. Moreover, fenofibrate treatment of T. cruzi-stimulated cells, increased the frequency of the non-classical subpopulation in Asy patients. Interestingly, fenofibrate restores CCR2 levels but does not modify HLA-DR expression in any groups. In conclusion, our results emphasize a potential role for fenofibrate as a modulator of monocyte subpopulations towards an anti-inflammatory and healing profile in different stages of chronic Chagas disease.
publishDate 2022
dc.date.none.fl_str_mv 2022-01
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/11336/211236
Pieralisi, Azul Victoria; Cevey, Ágata Carolina; Penas, Federico Nicolás; Prado, Nilda; Mori, Ana; et al.; Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC; Frontiers Media; Frontiers in Cellular and Infection Microbiology; 11; 1-2022; 1-15
2235-2988
CONICET Digital
CONICET
url http://hdl.handle.net/11336/211236
identifier_str_mv Pieralisi, Azul Victoria; Cevey, Ágata Carolina; Penas, Federico Nicolás; Prado, Nilda; Mori, Ana; et al.; Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC; Frontiers Media; Frontiers in Cellular and Infection Microbiology; 11; 1-2022; 1-15
2235-2988
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.3389/fcimb.2021.785166
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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