Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation
- Autores
- Genoula, Melanie; Marin Franco, Jose Luis; Dupont, Maeva; Kviatcovsky, Denise; Milillo, María Ayelén; Schierloh, Luis Pablo; Moraña, Eduardo Jose; Poggi, Susana; Palmero, Domingo; Mata Espinosa, Dulce; González Domínguez, Erika; Contreras, Juan Carlos León; Barrionuevo, Paula; Rearte, María Bárbara; Córdoba Moreno, Marlina Olyissa; Fontanals, Adriana Mirta; Crotta Asis, Agostina; Gago, Gabriela Marisa; Cougoule, Céline; Neyrolles, Olivier; Maridonneau Parini, Isabelle; Sánchez Torres, Carmen; Hernández Pando, Rogelio; Vérollet, Christel; Lugo Villarino, Geanncarlo; Sasiain, María del Carmen; Balboa, Luciana
- Año de publicación
- 2018
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection. We found that TB-PE induced FM differentiation as observed by the increase in lipid bodies, intracellular cholesterol, and expression of the scavenger receptor CD36, as well as the enzyme acyl CoA:cholesterol acyl transferase (ACAT). Importantly, interleukin-10 (IL-10) depletion from TB-PE prevented the augmentation of all these parameters. Moreover, we observed a positive correlation between the levels of IL-10 and the number of lipid-laden CD14+ cells among the pleural cells in TB patients, demonstrating that FM differentiation occurs within the pleural environment. Downstream of IL-10 signaling, we noticed that the transcription factor signal transducer and activator of transcription 3 was activated by TB-PE, and its chemical inhibition prevented the accumulation of lipid bodies and ACAT expression in macrophages. In terms of the host immune response, TB-PE-treated macrophages displayed immunosuppressive properties and bore higher bacillary loads. Finally, we confirmed our results using bone marrow-derived macrophage from IL-10-/- mice demonstrating that IL-10 deficiency partially prevented foamy phenotype induction after Mtb lipids exposure. In conclusion, our results evidence a role of IL-10 in promoting the differentiation of FM in the context of Mtb infection, contributing to our understanding of how alterations of the host metabolic factors may favor pathogen persistence.
Fil: Genoula, Melanie. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Marin Franco, Jose Luis. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. International Associated Laboratory; Argentina. Université Paul Sabatier; Francia
Fil: Dupont, Maeva. Université Paul Sabatier; Francia. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Argentina. International Associated Laboratory; Francia
Fil: Kviatcovsky, Denise. International Associated Laboratory; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; Argentina
Fil: Milillo, María Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Schierloh, Luis Pablo. International Associated Laboratory; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; Francia
Fil: Moraña, Eduardo Jose. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Poggi, Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Palmero, Domingo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Mata Espinosa, Dulce. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; México
Fil: González Domínguez, Erika. Instituto Politécnico Nacional; México
Fil: Contreras, Juan Carlos León. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; México
Fil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Córdoba Moreno, Marlina Olyissa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Fontanals, Adriana Mirta. Fundación Instituto Leloir; Argentina
Fil: Crotta Asis, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Gago, Gabriela Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Cougoule, Céline. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. International Associated Laboratory; Argentina
Fil: Neyrolles, Olivier. International Associated Laboratory; Francia. International Associated Laboratory; Argentina. Centre National de la Recherche Scientifique; Francia
Fil: Maridonneau Parini, Isabelle. International Associated Laboratory; Francia. International Associated Laboratory; Argentina. Centre National de la Recherche Scientifique; Francia
Fil: Sánchez Torres, Carmen. Instituto Politécnico Nacional; México
Fil: Hernández Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; México
Fil: Vérollet, Christel. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. International Associated Laboratory; Argentina
Fil: Lugo Villarino, Geanncarlo. International Associated Laboratory; Argentina. International Associated Laboratory; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; Francia. International Associated Laboratory; Argentina
Fil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; Argentina. International Associated Laboratory; Francia - Materia
-
ACAT
FOAMY MACROPHAGES
INTERLEUKIN-10
LIPIDS
SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3
TUBERCULOSIS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/95986
Ver los metadatos del registro completo
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Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulationGenoula, MelanieMarin Franco, Jose LuisDupont, MaevaKviatcovsky, DeniseMilillo, María AyelénSchierloh, Luis PabloMoraña, Eduardo JosePoggi, SusanaPalmero, DomingoMata Espinosa, DulceGonzález Domínguez, ErikaContreras, Juan Carlos LeónBarrionuevo, PaulaRearte, María BárbaraCórdoba Moreno, Marlina OlyissaFontanals, Adriana MirtaCrotta Asis, AgostinaGago, Gabriela MarisaCougoule, CélineNeyrolles, OlivierMaridonneau Parini, IsabelleSánchez Torres, CarmenHernández Pando, RogelioVérollet, ChristelLugo Villarino, GeanncarloSasiain, María del CarmenBalboa, LucianaACATFOAMY MACROPHAGESINTERLEUKIN-10LIPIDSSIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3TUBERCULOSIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection. We found that TB-PE induced FM differentiation as observed by the increase in lipid bodies, intracellular cholesterol, and expression of the scavenger receptor CD36, as well as the enzyme acyl CoA:cholesterol acyl transferase (ACAT). Importantly, interleukin-10 (IL-10) depletion from TB-PE prevented the augmentation of all these parameters. Moreover, we observed a positive correlation between the levels of IL-10 and the number of lipid-laden CD14+ cells among the pleural cells in TB patients, demonstrating that FM differentiation occurs within the pleural environment. Downstream of IL-10 signaling, we noticed that the transcription factor signal transducer and activator of transcription 3 was activated by TB-PE, and its chemical inhibition prevented the accumulation of lipid bodies and ACAT expression in macrophages. In terms of the host immune response, TB-PE-treated macrophages displayed immunosuppressive properties and bore higher bacillary loads. Finally, we confirmed our results using bone marrow-derived macrophage from IL-10-/- mice demonstrating that IL-10 deficiency partially prevented foamy phenotype induction after Mtb lipids exposure. In conclusion, our results evidence a role of IL-10 in promoting the differentiation of FM in the context of Mtb infection, contributing to our understanding of how alterations of the host metabolic factors may favor pathogen persistence.Fil: Genoula, Melanie. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Marin Franco, Jose Luis. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. International Associated Laboratory; Argentina. Université Paul Sabatier; FranciaFil: Dupont, Maeva. Université Paul Sabatier; Francia. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Argentina. International Associated Laboratory; FranciaFil: Kviatcovsky, Denise. International Associated Laboratory; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; ArgentinaFil: Milillo, María Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Schierloh, Luis Pablo. International Associated Laboratory; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; FranciaFil: Moraña, Eduardo Jose. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Poggi, Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Palmero, Domingo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Mata Espinosa, Dulce. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; MéxicoFil: González Domínguez, Erika. Instituto Politécnico Nacional; MéxicoFil: Contreras, Juan Carlos León. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; MéxicoFil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Córdoba Moreno, Marlina Olyissa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fontanals, Adriana Mirta. Fundación Instituto Leloir; ArgentinaFil: Crotta Asis, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Gago, Gabriela Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Cougoule, Céline. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. International Associated Laboratory; ArgentinaFil: Neyrolles, Olivier. International Associated Laboratory; Francia. International Associated Laboratory; Argentina. Centre National de la Recherche Scientifique; FranciaFil: Maridonneau Parini, Isabelle. International Associated Laboratory; Francia. International Associated Laboratory; Argentina. Centre National de la Recherche Scientifique; FranciaFil: Sánchez Torres, Carmen. Instituto Politécnico Nacional; MéxicoFil: Hernández Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; MéxicoFil: Vérollet, Christel. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. International Associated Laboratory; ArgentinaFil: Lugo Villarino, Geanncarlo. International Associated Laboratory; Argentina. International Associated Laboratory; Francia. Centre National de la Recherche Scientifique; FranciaFil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; Francia. International Associated Laboratory; ArgentinaFil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; Argentina. International Associated Laboratory; FranciaFrontiers Media S.A.2018-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95986Genoula, Melanie; Marin Franco, Jose Luis; Dupont, Maeva; Kviatcovsky, Denise; Milillo, María Ayelén; et al.; Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation; Frontiers Media S.A.; Frontiers in Immunology; 9; 3-2018; 1-171664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fimmu.2018.00459/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.00459info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:07:16Zoai:ri.conicet.gov.ar:11336/95986instacron: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 12:07:16.409CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation |
| title |
Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation |
| spellingShingle |
Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation Genoula, Melanie ACAT FOAMY MACROPHAGES INTERLEUKIN-10 LIPIDS SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3 TUBERCULOSIS |
| title_short |
Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation |
| title_full |
Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation |
| title_fullStr |
Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation |
| title_full_unstemmed |
Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation |
| title_sort |
Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation |
| dc.creator.none.fl_str_mv |
Genoula, Melanie Marin Franco, Jose Luis Dupont, Maeva Kviatcovsky, Denise Milillo, María Ayelén Schierloh, Luis Pablo Moraña, Eduardo Jose Poggi, Susana Palmero, Domingo Mata Espinosa, Dulce González Domínguez, Erika Contreras, Juan Carlos León Barrionuevo, Paula Rearte, María Bárbara Córdoba Moreno, Marlina Olyissa Fontanals, Adriana Mirta Crotta Asis, Agostina Gago, Gabriela Marisa Cougoule, Céline Neyrolles, Olivier Maridonneau Parini, Isabelle Sánchez Torres, Carmen Hernández Pando, Rogelio Vérollet, Christel Lugo Villarino, Geanncarlo Sasiain, María del Carmen Balboa, Luciana |
| author |
Genoula, Melanie |
| author_facet |
Genoula, Melanie Marin Franco, Jose Luis Dupont, Maeva Kviatcovsky, Denise Milillo, María Ayelén Schierloh, Luis Pablo Moraña, Eduardo Jose Poggi, Susana Palmero, Domingo Mata Espinosa, Dulce González Domínguez, Erika Contreras, Juan Carlos León Barrionuevo, Paula Rearte, María Bárbara Córdoba Moreno, Marlina Olyissa Fontanals, Adriana Mirta Crotta Asis, Agostina Gago, Gabriela Marisa Cougoule, Céline Neyrolles, Olivier Maridonneau Parini, Isabelle Sánchez Torres, Carmen Hernández Pando, Rogelio Vérollet, Christel Lugo Villarino, Geanncarlo Sasiain, María del Carmen Balboa, Luciana |
| author_role |
author |
| author2 |
Marin Franco, Jose Luis Dupont, Maeva Kviatcovsky, Denise Milillo, María Ayelén Schierloh, Luis Pablo Moraña, Eduardo Jose Poggi, Susana Palmero, Domingo Mata Espinosa, Dulce González Domínguez, Erika Contreras, Juan Carlos León Barrionuevo, Paula Rearte, María Bárbara Córdoba Moreno, Marlina Olyissa Fontanals, Adriana Mirta Crotta Asis, Agostina Gago, Gabriela Marisa Cougoule, Céline Neyrolles, Olivier Maridonneau Parini, Isabelle Sánchez Torres, Carmen Hernández Pando, Rogelio Vérollet, Christel Lugo Villarino, Geanncarlo Sasiain, María del Carmen Balboa, Luciana |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
ACAT FOAMY MACROPHAGES INTERLEUKIN-10 LIPIDS SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3 TUBERCULOSIS |
| topic |
ACAT FOAMY MACROPHAGES INTERLEUKIN-10 LIPIDS SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3 TUBERCULOSIS |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection. We found that TB-PE induced FM differentiation as observed by the increase in lipid bodies, intracellular cholesterol, and expression of the scavenger receptor CD36, as well as the enzyme acyl CoA:cholesterol acyl transferase (ACAT). Importantly, interleukin-10 (IL-10) depletion from TB-PE prevented the augmentation of all these parameters. Moreover, we observed a positive correlation between the levels of IL-10 and the number of lipid-laden CD14+ cells among the pleural cells in TB patients, demonstrating that FM differentiation occurs within the pleural environment. Downstream of IL-10 signaling, we noticed that the transcription factor signal transducer and activator of transcription 3 was activated by TB-PE, and its chemical inhibition prevented the accumulation of lipid bodies and ACAT expression in macrophages. In terms of the host immune response, TB-PE-treated macrophages displayed immunosuppressive properties and bore higher bacillary loads. Finally, we confirmed our results using bone marrow-derived macrophage from IL-10-/- mice demonstrating that IL-10 deficiency partially prevented foamy phenotype induction after Mtb lipids exposure. In conclusion, our results evidence a role of IL-10 in promoting the differentiation of FM in the context of Mtb infection, contributing to our understanding of how alterations of the host metabolic factors may favor pathogen persistence. Fil: Genoula, Melanie. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Marin Franco, Jose Luis. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. International Associated Laboratory; Argentina. Université Paul Sabatier; Francia Fil: Dupont, Maeva. Université Paul Sabatier; Francia. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Argentina. International Associated Laboratory; Francia Fil: Kviatcovsky, Denise. International Associated Laboratory; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; Argentina Fil: Milillo, María Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Schierloh, Luis Pablo. International Associated Laboratory; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; Francia Fil: Moraña, Eduardo Jose. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Poggi, Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Palmero, Domingo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Mata Espinosa, Dulce. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; México Fil: González Domínguez, Erika. Instituto Politécnico Nacional; México Fil: Contreras, Juan Carlos León. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; México Fil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Córdoba Moreno, Marlina Olyissa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Fontanals, Adriana Mirta. Fundación Instituto Leloir; Argentina Fil: Crotta Asis, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Gago, Gabriela Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Cougoule, Céline. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. International Associated Laboratory; Argentina Fil: Neyrolles, Olivier. International Associated Laboratory; Francia. International Associated Laboratory; Argentina. Centre National de la Recherche Scientifique; Francia Fil: Maridonneau Parini, Isabelle. International Associated Laboratory; Francia. International Associated Laboratory; Argentina. Centre National de la Recherche Scientifique; Francia Fil: Sánchez Torres, Carmen. Instituto Politécnico Nacional; México Fil: Hernández Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; México Fil: Vérollet, Christel. Centre National de la Recherche Scientifique; Francia. International Associated Laboratory; Francia. International Associated Laboratory; Argentina Fil: Lugo Villarino, Geanncarlo. International Associated Laboratory; Argentina. International Associated Laboratory; Francia. Centre National de la Recherche Scientifique; Francia Fil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; Francia. International Associated Laboratory; Argentina Fil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. International Associated Laboratory; Argentina. International Associated Laboratory; Francia |
| description |
The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection. We found that TB-PE induced FM differentiation as observed by the increase in lipid bodies, intracellular cholesterol, and expression of the scavenger receptor CD36, as well as the enzyme acyl CoA:cholesterol acyl transferase (ACAT). Importantly, interleukin-10 (IL-10) depletion from TB-PE prevented the augmentation of all these parameters. Moreover, we observed a positive correlation between the levels of IL-10 and the number of lipid-laden CD14+ cells among the pleural cells in TB patients, demonstrating that FM differentiation occurs within the pleural environment. Downstream of IL-10 signaling, we noticed that the transcription factor signal transducer and activator of transcription 3 was activated by TB-PE, and its chemical inhibition prevented the accumulation of lipid bodies and ACAT expression in macrophages. In terms of the host immune response, TB-PE-treated macrophages displayed immunosuppressive properties and bore higher bacillary loads. Finally, we confirmed our results using bone marrow-derived macrophage from IL-10-/- mice demonstrating that IL-10 deficiency partially prevented foamy phenotype induction after Mtb lipids exposure. In conclusion, our results evidence a role of IL-10 in promoting the differentiation of FM in the context of Mtb infection, contributing to our understanding of how alterations of the host metabolic factors may favor pathogen persistence. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018-03 |
| 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/11336/95986 Genoula, Melanie; Marin Franco, Jose Luis; Dupont, Maeva; Kviatcovsky, Denise; Milillo, María Ayelén; et al.; Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation; Frontiers Media S.A.; Frontiers in Immunology; 9; 3-2018; 1-17 1664-3224 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/95986 |
| identifier_str_mv |
Genoula, Melanie; Marin Franco, Jose Luis; Dupont, Maeva; Kviatcovsky, Denise; Milillo, María Ayelén; et al.; Formation of foamy macrophages by tuberculous pleural effusions is triggered by the interleukin-10/signal transducer and activator of transcription 3 axis through ACAT upregulation; Frontiers Media S.A.; Frontiers in Immunology; 9; 3-2018; 1-17 1664-3224 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fimmu.2018.00459/full info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.00459 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
| eu_rights_str_mv |
openAccess |
| rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
| dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Frontiers Media S.A. |
| publisher.none.fl_str_mv |
Frontiers Media S.A. |
| dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
| reponame_str |
CONICET Digital (CONICET) |
| collection |
CONICET Digital (CONICET) |
| instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
| _version_ |
1846782436108664832 |
| score |
12.982451 |