Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria

Autores
Gómez, Sonia Alejandra; Arguelles, Claudia L.; Guerrieri, Diego; Tateosian, Nancy Liliana; Amiano, Nicolás Oscar; Slimovich, Rut; Maffia, Paulo Cesar; Abbate, Pablo Eduardo; Musella, Rosa María; García, Verónica Edith; Chuluyan, Hector Eduardo
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Rationale: Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity against pathogens such as Escherichia coli and Streptococcus. Furthermore, it has been reported that murine SLPI shows potent antimycobacterial activity. Objectives: The aim of the present study was to investigate whether human recombinant SLPI not only kills mycobacteria but also acts as a pattern recognition receptor for the host immune system. Methods: For the in vivo experiment, BALB/c mice were infected by intranasal instillation with Mycobacterium bovis BCG and viable BCG load in lung homogenates was later determined. For the in vitro experiments, SLPI was incubated overnight with a suspension of M. bovis BCG or the virulent strain Mycobacterium tuberculosis H37Rv, and the percentage survival as well as the binding of SLPI to mycobacteria was determined. Furthermore, bacteria phagocytosis was also determined by flow cytometry. Measurements and Main Results: Intranasal SLPI treatment decreased the number of colony-forming units recovered from lung homogenates, indicating that SLPI interfered with M. bovis BCG infection. Moreover, SLPI decreased the viability of both M. bovis BCG and H37Rv. We demonstrated that SLPI attached to the surface of the mycobacteria by binding to pathogen-associated molecular pattern mannan-capped lipoarabinomannans and phosphatidylinositol mannoside. Furthermore, we found that in the sputum of patients with tuberculosis, mycobacteria were coated with endogenous SLPI. Finally, we showed that phagocytosis of SLPI-coated mycobacteria was faster than that of uncoated bacteria. Conclusions: The present results demonstrate for the first time that human SLPI kills mycobacteria and is a new pattern recognition receptor for them.
Fil: Gómez, Sonia Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Arguelles, Claudia L.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina
Fil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina
Fil: Tateosian, Nancy Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Amiano, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina
Fil: Slimovich, Rut. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina
Fil: Maffia, Paulo Cesar. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Abbate, Pablo Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: García, Verónica Edith. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chuluyan, Hector Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Phagocytosis
Secretory Leukocyte Protease Inhibitor
Tuberculosis
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:11336/71408
Acceder
id CONICETDig_771af407ff708e3558d3abb4ce85dacc
oai_identifier_str oai:ri.conicet.gov.ar:11336/71408
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteriaGómez, Sonia AlejandraArguelles, Claudia L.Guerrieri, DiegoTateosian, Nancy LilianaAmiano, Nicolás OscarSlimovich, RutMaffia, Paulo CesarAbbate, Pablo EduardoMusella, Rosa MaríaGarcía, Verónica EdithChuluyan, Hector EduardoPhagocytosisSecretory Leukocyte Protease InhibitorTuberculosishttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Rationale: Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity against pathogens such as Escherichia coli and Streptococcus. Furthermore, it has been reported that murine SLPI shows potent antimycobacterial activity. Objectives: The aim of the present study was to investigate whether human recombinant SLPI not only kills mycobacteria but also acts as a pattern recognition receptor for the host immune system. Methods: For the in vivo experiment, BALB/c mice were infected by intranasal instillation with Mycobacterium bovis BCG and viable BCG load in lung homogenates was later determined. For the in vitro experiments, SLPI was incubated overnight with a suspension of M. bovis BCG or the virulent strain Mycobacterium tuberculosis H37Rv, and the percentage survival as well as the binding of SLPI to mycobacteria was determined. Furthermore, bacteria phagocytosis was also determined by flow cytometry. Measurements and Main Results: Intranasal SLPI treatment decreased the number of colony-forming units recovered from lung homogenates, indicating that SLPI interfered with M. bovis BCG infection. Moreover, SLPI decreased the viability of both M. bovis BCG and H37Rv. We demonstrated that SLPI attached to the surface of the mycobacteria by binding to pathogen-associated molecular pattern mannan-capped lipoarabinomannans and phosphatidylinositol mannoside. Furthermore, we found that in the sputum of patients with tuberculosis, mycobacteria were coated with endogenous SLPI. Finally, we showed that phagocytosis of SLPI-coated mycobacteria was faster than that of uncoated bacteria. Conclusions: The present results demonstrate for the first time that human SLPI kills mycobacteria and is a new pattern recognition receptor for them.Fil: Gómez, Sonia Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Arguelles, Claudia L.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; ArgentinaFil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; ArgentinaFil: Tateosian, Nancy Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Amiano, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; ArgentinaFil: Slimovich, Rut. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; ArgentinaFil: Maffia, Paulo Cesar. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Abbate, Pablo Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: García, Verónica Edith. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chuluyan, Hector Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Thoracic Society2009-02info: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/pdfhttp://hdl.handle.net/11336/71408Gómez, Sonia Alejandra; Arguelles, Claudia L.; Guerrieri, Diego; Tateosian, Nancy Liliana; Amiano, Nicolás Oscar; et al.; Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria; American Thoracic Society; American Journal of Respiratory and Critical Care Medicine; 179; 3; 2-2009; 247-2531073-449XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.atsjournals.org/doi/full/10.1164/rccm.200804-615OCinfo:eu-repo/semantics/altIdentifier/doi/10.1164/rccm.200804-615OCinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:23:13Zoai:ri.conicet.gov.ar:11336/71408instacron: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:34982025-09-10 13:23:14.008CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria
title Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria
spellingShingle Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria
Gómez, Sonia Alejandra
Phagocytosis
Secretory Leukocyte Protease Inhibitor
Tuberculosis
title_short Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria
title_full Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria
title_fullStr Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria
title_full_unstemmed Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria
title_sort Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria
dc.creator.none.fl_str_mv Gómez, Sonia Alejandra
Arguelles, Claudia L.
Guerrieri, Diego
Tateosian, Nancy Liliana
Amiano, Nicolás Oscar
Slimovich, Rut
Maffia, Paulo Cesar
Abbate, Pablo Eduardo
Musella, Rosa María
García, Verónica Edith
Chuluyan, Hector Eduardo
author Gómez, Sonia Alejandra
author_facet Gómez, Sonia Alejandra
Arguelles, Claudia L.
Guerrieri, Diego
Tateosian, Nancy Liliana
Amiano, Nicolás Oscar
Slimovich, Rut
Maffia, Paulo Cesar
Abbate, Pablo Eduardo
Musella, Rosa María
García, Verónica Edith
Chuluyan, Hector Eduardo
author_role author
author2 Arguelles, Claudia L.
Guerrieri, Diego
Tateosian, Nancy Liliana
Amiano, Nicolás Oscar
Slimovich, Rut
Maffia, Paulo Cesar
Abbate, Pablo Eduardo
Musella, Rosa María
García, Verónica Edith
Chuluyan, Hector Eduardo
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Phagocytosis
Secretory Leukocyte Protease Inhibitor
Tuberculosis
topic Phagocytosis
Secretory Leukocyte Protease Inhibitor
Tuberculosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Rationale: Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity against pathogens such as Escherichia coli and Streptococcus. Furthermore, it has been reported that murine SLPI shows potent antimycobacterial activity. Objectives: The aim of the present study was to investigate whether human recombinant SLPI not only kills mycobacteria but also acts as a pattern recognition receptor for the host immune system. Methods: For the in vivo experiment, BALB/c mice were infected by intranasal instillation with Mycobacterium bovis BCG and viable BCG load in lung homogenates was later determined. For the in vitro experiments, SLPI was incubated overnight with a suspension of M. bovis BCG or the virulent strain Mycobacterium tuberculosis H37Rv, and the percentage survival as well as the binding of SLPI to mycobacteria was determined. Furthermore, bacteria phagocytosis was also determined by flow cytometry. Measurements and Main Results: Intranasal SLPI treatment decreased the number of colony-forming units recovered from lung homogenates, indicating that SLPI interfered with M. bovis BCG infection. Moreover, SLPI decreased the viability of both M. bovis BCG and H37Rv. We demonstrated that SLPI attached to the surface of the mycobacteria by binding to pathogen-associated molecular pattern mannan-capped lipoarabinomannans and phosphatidylinositol mannoside. Furthermore, we found that in the sputum of patients with tuberculosis, mycobacteria were coated with endogenous SLPI. Finally, we showed that phagocytosis of SLPI-coated mycobacteria was faster than that of uncoated bacteria. Conclusions: The present results demonstrate for the first time that human SLPI kills mycobacteria and is a new pattern recognition receptor for them.
Fil: Gómez, Sonia Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Arguelles, Claudia L.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina
Fil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina
Fil: Tateosian, Nancy Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Amiano, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina
Fil: Slimovich, Rut. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina
Fil: Maffia, Paulo Cesar. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Abbate, Pablo Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: García, Verónica Edith. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chuluyan, Hector Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Rationale: Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity against pathogens such as Escherichia coli and Streptococcus. Furthermore, it has been reported that murine SLPI shows potent antimycobacterial activity. Objectives: The aim of the present study was to investigate whether human recombinant SLPI not only kills mycobacteria but also acts as a pattern recognition receptor for the host immune system. Methods: For the in vivo experiment, BALB/c mice were infected by intranasal instillation with Mycobacterium bovis BCG and viable BCG load in lung homogenates was later determined. For the in vitro experiments, SLPI was incubated overnight with a suspension of M. bovis BCG or the virulent strain Mycobacterium tuberculosis H37Rv, and the percentage survival as well as the binding of SLPI to mycobacteria was determined. Furthermore, bacteria phagocytosis was also determined by flow cytometry. Measurements and Main Results: Intranasal SLPI treatment decreased the number of colony-forming units recovered from lung homogenates, indicating that SLPI interfered with M. bovis BCG infection. Moreover, SLPI decreased the viability of both M. bovis BCG and H37Rv. We demonstrated that SLPI attached to the surface of the mycobacteria by binding to pathogen-associated molecular pattern mannan-capped lipoarabinomannans and phosphatidylinositol mannoside. Furthermore, we found that in the sputum of patients with tuberculosis, mycobacteria were coated with endogenous SLPI. Finally, we showed that phagocytosis of SLPI-coated mycobacteria was faster than that of uncoated bacteria. Conclusions: The present results demonstrate for the first time that human SLPI kills mycobacteria and is a new pattern recognition receptor for them.
publishDate 2009
dc.date.none.fl_str_mv 2009-02
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/11336/71408
Gómez, Sonia Alejandra; Arguelles, Claudia L.; Guerrieri, Diego; Tateosian, Nancy Liliana; Amiano, Nicolás Oscar; et al.; Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria; American Thoracic Society; American Journal of Respiratory and Critical Care Medicine; 179; 3; 2-2009; 247-253
1073-449X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/71408
identifier_str_mv Gómez, Sonia Alejandra; Arguelles, Claudia L.; Guerrieri, Diego; Tateosian, Nancy Liliana; Amiano, Nicolás Oscar; et al.; Secretory leukocyte protease inhibitor a secreted pattern recognition receptor for mycobacteria; American Thoracic Society; American Journal of Respiratory and Critical Care Medicine; 179; 3; 2-2009; 247-253
1073-449X
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.atsjournals.org/doi/full/10.1164/rccm.200804-615OC
info:eu-repo/semantics/altIdentifier/doi/10.1164/rccm.200804-615OC
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
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application/pdf
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dc.publisher.none.fl_str_mv American Thoracic Society
publisher.none.fl_str_mv American Thoracic Society
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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