The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis
- Autores
- Islas Weinstein, Leon; Marquina Castillo, Brenda; Mata Espinosa, Dulce; Paredes González, Iris S.; Chávez, Jaime; Balboa, Luciana; Marin Franco, Jose Luis; Guerrero Romero, Daniel; Barrios Payan, Jorge Alberto; Hernandez Pando, Rogelio
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The cholinergic system is present in both bacteria and mammals and regulates inflammation during bacterial respiratory infections through neuronal and non-neuronal production of acetylcholine (ACh) and its receptors. However, the presence of this system during the immunopathogenesis of pulmonary tuberculosis (TB) in vivo and in its causative agent Mycobacterium tuberculosis (Mtb) has not been studied. Therefore, we used an experimental model of progressive pulmonary TB in BALB/c mice to quantify pulmonary ACh using high-performance liquid chromatography during the course of the disease. In addition, we performed immunohistochemistry in lung tissue to determine the cellular expression of cholinergic system components, and then administered nicotinic receptor (nAChR) antagonists to validate their effect on lung bacterial burden, inflammation, and pro-inflammatory cytokines. Finally, we subjected Mtb cultures to colorimetric analysis to reveal the production of ACh and the effect of ACh and nAChR antagonists on Mtb growth. Our results show high concentrations of ACh and expression of its synthesizing enzyme choline acetyltransferase (ChAT) during early infection in lung epithelial cells and macrophages. During late progressive TB, lung ACh upregulation was even higher and coincided with ChAT and α7 nAChR subunit expression in immune cells. Moreover, the administration of nAChR antagonists increased pro-inflammatory cytokines, reduced bacillary loads and synergized with antibiotic therapy in multidrug resistant TB. Finally, in vitro studies revealed that the bacteria is capable of producing nanomolar concentrations of ACh in liquid culture. In addition, the administration of ACh and nicotinic antagonists to Mtb cultures induced or inhibited bacterial proliferation, respectively. These results suggest that Mtb possesses a cholinergic system and upregulates the lung non-neuronal cholinergic system, particularly during late progressive TB. The upregulation of the cholinergic system during infection could aid both bacterial growth and immunomodulation within the lung to favor disease progression. Furthermore, the therapeutic efficacy of modulating this system suggests that it could be a target for treating the disease.
Fil: Islas Weinstein, Leon. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México
Fil: Marquina Castillo, Brenda. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México
Fil: Mata Espinosa, Dulce. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México
Fil: Paredes González, Iris S.. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México
Fil: Chávez, Jaime. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México
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
Fil: Marin Franco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Guerrero Romero, Daniel. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México
Fil: Barrios Payan, Jorge Alberto. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México
Fil: Hernandez Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México - Materia
-
ACETYLCHOLINE
CHOLINERGIC SYSTEM
MYCOBACTERIUM TUBERCULOSIS
TUBERCULOSIS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/156682
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The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary TuberculosisIslas Weinstein, LeonMarquina Castillo, BrendaMata Espinosa, DulceParedes González, Iris S.Chávez, JaimeBalboa, LucianaMarin Franco, Jose LuisGuerrero Romero, DanielBarrios Payan, Jorge AlbertoHernandez Pando, RogelioACETYLCHOLINECHOLINERGIC SYSTEMMYCOBACTERIUM TUBERCULOSISTUBERCULOSIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The cholinergic system is present in both bacteria and mammals and regulates inflammation during bacterial respiratory infections through neuronal and non-neuronal production of acetylcholine (ACh) and its receptors. However, the presence of this system during the immunopathogenesis of pulmonary tuberculosis (TB) in vivo and in its causative agent Mycobacterium tuberculosis (Mtb) has not been studied. Therefore, we used an experimental model of progressive pulmonary TB in BALB/c mice to quantify pulmonary ACh using high-performance liquid chromatography during the course of the disease. In addition, we performed immunohistochemistry in lung tissue to determine the cellular expression of cholinergic system components, and then administered nicotinic receptor (nAChR) antagonists to validate their effect on lung bacterial burden, inflammation, and pro-inflammatory cytokines. Finally, we subjected Mtb cultures to colorimetric analysis to reveal the production of ACh and the effect of ACh and nAChR antagonists on Mtb growth. Our results show high concentrations of ACh and expression of its synthesizing enzyme choline acetyltransferase (ChAT) during early infection in lung epithelial cells and macrophages. During late progressive TB, lung ACh upregulation was even higher and coincided with ChAT and α7 nAChR subunit expression in immune cells. Moreover, the administration of nAChR antagonists increased pro-inflammatory cytokines, reduced bacillary loads and synergized with antibiotic therapy in multidrug resistant TB. Finally, in vitro studies revealed that the bacteria is capable of producing nanomolar concentrations of ACh in liquid culture. In addition, the administration of ACh and nicotinic antagonists to Mtb cultures induced or inhibited bacterial proliferation, respectively. These results suggest that Mtb possesses a cholinergic system and upregulates the lung non-neuronal cholinergic system, particularly during late progressive TB. The upregulation of the cholinergic system during infection could aid both bacterial growth and immunomodulation within the lung to favor disease progression. Furthermore, the therapeutic efficacy of modulating this system suggests that it could be a target for treating the disease.Fil: Islas Weinstein, Leon. Instituto Nacional de Ciencias Médicas y Nutrición Sz; MéxicoFil: Marquina Castillo, Brenda. Instituto Nacional de Ciencias Médicas y Nutrición Sz; MéxicoFil: Mata Espinosa, Dulce. Instituto Nacional de Ciencias Médicas y Nutrición Sz; MéxicoFil: Paredes González, Iris S.. Instituto Nacional de Ciencias Médicas y Nutrición Sz; MéxicoFil: Chávez, Jaime. Instituto Nacional de Ciencias Médicas y Nutrición Sz; MéxicoFil: Balboa, Luciana. 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. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Guerrero Romero, Daniel. Instituto Nacional de Ciencias Médicas y Nutrición Sz; MéxicoFil: Barrios Payan, Jorge Alberto. Instituto Nacional de Ciencias Médicas y Nutrición Sz; MéxicoFil: Hernandez Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición Sz; MéxicoFrontiers Research Foundation2021-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/156682Islas Weinstein, Leon; Marquina Castillo, Brenda; Mata Espinosa, Dulce; Paredes González, Iris S.; Chávez, Jaime; et al.; The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis; Frontiers Research Foundation; Frontiers in immunology; 11; 2-2021; 1-141664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2020.581911/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2020.581911info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:01Zoai:ri.conicet.gov.ar:11336/156682instacron: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:34982025-09-03 09:57:02.032CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis |
title |
The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis |
spellingShingle |
The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis Islas Weinstein, Leon ACETYLCHOLINE CHOLINERGIC SYSTEM MYCOBACTERIUM TUBERCULOSIS TUBERCULOSIS |
title_short |
The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis |
title_full |
The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis |
title_fullStr |
The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis |
title_full_unstemmed |
The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis |
title_sort |
The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis |
dc.creator.none.fl_str_mv |
Islas Weinstein, Leon Marquina Castillo, Brenda Mata Espinosa, Dulce Paredes González, Iris S. Chávez, Jaime Balboa, Luciana Marin Franco, Jose Luis Guerrero Romero, Daniel Barrios Payan, Jorge Alberto Hernandez Pando, Rogelio |
author |
Islas Weinstein, Leon |
author_facet |
Islas Weinstein, Leon Marquina Castillo, Brenda Mata Espinosa, Dulce Paredes González, Iris S. Chávez, Jaime Balboa, Luciana Marin Franco, Jose Luis Guerrero Romero, Daniel Barrios Payan, Jorge Alberto Hernandez Pando, Rogelio |
author_role |
author |
author2 |
Marquina Castillo, Brenda Mata Espinosa, Dulce Paredes González, Iris S. Chávez, Jaime Balboa, Luciana Marin Franco, Jose Luis Guerrero Romero, Daniel Barrios Payan, Jorge Alberto Hernandez Pando, Rogelio |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
ACETYLCHOLINE CHOLINERGIC SYSTEM MYCOBACTERIUM TUBERCULOSIS TUBERCULOSIS |
topic |
ACETYLCHOLINE CHOLINERGIC SYSTEM MYCOBACTERIUM TUBERCULOSIS 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 cholinergic system is present in both bacteria and mammals and regulates inflammation during bacterial respiratory infections through neuronal and non-neuronal production of acetylcholine (ACh) and its receptors. However, the presence of this system during the immunopathogenesis of pulmonary tuberculosis (TB) in vivo and in its causative agent Mycobacterium tuberculosis (Mtb) has not been studied. Therefore, we used an experimental model of progressive pulmonary TB in BALB/c mice to quantify pulmonary ACh using high-performance liquid chromatography during the course of the disease. In addition, we performed immunohistochemistry in lung tissue to determine the cellular expression of cholinergic system components, and then administered nicotinic receptor (nAChR) antagonists to validate their effect on lung bacterial burden, inflammation, and pro-inflammatory cytokines. Finally, we subjected Mtb cultures to colorimetric analysis to reveal the production of ACh and the effect of ACh and nAChR antagonists on Mtb growth. Our results show high concentrations of ACh and expression of its synthesizing enzyme choline acetyltransferase (ChAT) during early infection in lung epithelial cells and macrophages. During late progressive TB, lung ACh upregulation was even higher and coincided with ChAT and α7 nAChR subunit expression in immune cells. Moreover, the administration of nAChR antagonists increased pro-inflammatory cytokines, reduced bacillary loads and synergized with antibiotic therapy in multidrug resistant TB. Finally, in vitro studies revealed that the bacteria is capable of producing nanomolar concentrations of ACh in liquid culture. In addition, the administration of ACh and nicotinic antagonists to Mtb cultures induced or inhibited bacterial proliferation, respectively. These results suggest that Mtb possesses a cholinergic system and upregulates the lung non-neuronal cholinergic system, particularly during late progressive TB. The upregulation of the cholinergic system during infection could aid both bacterial growth and immunomodulation within the lung to favor disease progression. Furthermore, the therapeutic efficacy of modulating this system suggests that it could be a target for treating the disease. Fil: Islas Weinstein, Leon. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México Fil: Marquina Castillo, Brenda. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México Fil: Mata Espinosa, Dulce. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México Fil: Paredes González, Iris S.. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México Fil: Chávez, Jaime. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México 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 Fil: Marin Franco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Guerrero Romero, Daniel. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México Fil: Barrios Payan, Jorge Alberto. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México Fil: Hernandez Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición Sz; México |
description |
The cholinergic system is present in both bacteria and mammals and regulates inflammation during bacterial respiratory infections through neuronal and non-neuronal production of acetylcholine (ACh) and its receptors. However, the presence of this system during the immunopathogenesis of pulmonary tuberculosis (TB) in vivo and in its causative agent Mycobacterium tuberculosis (Mtb) has not been studied. Therefore, we used an experimental model of progressive pulmonary TB in BALB/c mice to quantify pulmonary ACh using high-performance liquid chromatography during the course of the disease. In addition, we performed immunohistochemistry in lung tissue to determine the cellular expression of cholinergic system components, and then administered nicotinic receptor (nAChR) antagonists to validate their effect on lung bacterial burden, inflammation, and pro-inflammatory cytokines. Finally, we subjected Mtb cultures to colorimetric analysis to reveal the production of ACh and the effect of ACh and nAChR antagonists on Mtb growth. Our results show high concentrations of ACh and expression of its synthesizing enzyme choline acetyltransferase (ChAT) during early infection in lung epithelial cells and macrophages. During late progressive TB, lung ACh upregulation was even higher and coincided with ChAT and α7 nAChR subunit expression in immune cells. Moreover, the administration of nAChR antagonists increased pro-inflammatory cytokines, reduced bacillary loads and synergized with antibiotic therapy in multidrug resistant TB. Finally, in vitro studies revealed that the bacteria is capable of producing nanomolar concentrations of ACh in liquid culture. In addition, the administration of ACh and nicotinic antagonists to Mtb cultures induced or inhibited bacterial proliferation, respectively. These results suggest that Mtb possesses a cholinergic system and upregulates the lung non-neuronal cholinergic system, particularly during late progressive TB. The upregulation of the cholinergic system during infection could aid both bacterial growth and immunomodulation within the lung to favor disease progression. Furthermore, the therapeutic efficacy of modulating this system suggests that it could be a target for treating the disease. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-02 |
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/11336/156682 Islas Weinstein, Leon; Marquina Castillo, Brenda; Mata Espinosa, Dulce; Paredes González, Iris S.; Chávez, Jaime; et al.; The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis; Frontiers Research Foundation; Frontiers in immunology; 11; 2-2021; 1-14 1664-3224 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/156682 |
identifier_str_mv |
Islas Weinstein, Leon; Marquina Castillo, Brenda; Mata Espinosa, Dulce; Paredes González, Iris S.; Chávez, Jaime; et al.; The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis; Frontiers Research Foundation; Frontiers in immunology; 11; 2-2021; 1-14 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/https://www.frontiersin.org/articles/10.3389/fimmu.2020.581911/full info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2020.581911 |
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 |
dc.publisher.none.fl_str_mv |
Frontiers Research Foundation |
publisher.none.fl_str_mv |
Frontiers Research Foundation |
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 |
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1842269435364114432 |
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13.13397 |