On the killing of mycobacteria by macrophages

Autores
Jordao, Luisa; Bleck, Christopher K.; Mayorga, Luis Segundo; Griffiths, Gareth; Anes, Elsa
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Both pathogenic and non-pathogenic mycobacteria are internalized into macrophagephagosomes. Whereas the non-pathogenic types are invariably killed by allmacrophages, the pathogens generally survive and grow. Here, we addressed thesurvival, production of nitrogen intermediates (RNI) and intracellular trafficking of thenon-pathogenic M. smegmatis, the pathogen-like, BCG and the pathogenic M. bovis indifferent mouse, human and bovine macrophages. The bacteriocidal effects of RNI wererestricted for all bacterial species to the early stages of infection. EM analysis showedclearly that all the mycobacteria remained within phagosomes even at late times ofinfection. The fraction of BCG and M. bovis found in mature phagolysosomes rarelyexceeded 10 % of total, irrespective of whether bacteria were growing, latent or beingkilled, with little correlation between the extent of phagosome maturation and thedegree of killing. Theoretical modelling of our data identified two different potentialsets of explanations that are consistent with our results. The model we favour is one inwhich a small but significant fraction of BCG is killed in an early phagosome, thenmaturation of a small fraction of phagosomes with both live and killed bacteria,followed by extremely rapid killing and digestion of the bacteria in phago-lysosomes.
Fil: Jordao, Luisa. Universidad de Lisboa. Facultad de Farmacia; Portugal
Fil: Bleck, Christopher K.. European Molecular Biology Laboratory; Alemania
Fil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. European Molecular Biology Laboratory; Alemania
Fil: Griffiths, Gareth. European Molecular Biology Laboratory; Alemania
Fil: Anes, Elsa. Universidad de Lisboa. Facultad de Farmacia; Portugal
Materia
Mathematical model
Macrophage
Mycobacterium
Phagosome
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:11336/127532
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/127532
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling On the killing of mycobacteria by macrophagesJordao, LuisaBleck, Christopher K.Mayorga, Luis SegundoGriffiths, GarethAnes, ElsaMathematical modelMacrophageMycobacteriumPhagosomehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Both pathogenic and non-pathogenic mycobacteria are internalized into macrophagephagosomes. Whereas the non-pathogenic types are invariably killed by allmacrophages, the pathogens generally survive and grow. Here, we addressed thesurvival, production of nitrogen intermediates (RNI) and intracellular trafficking of thenon-pathogenic M. smegmatis, the pathogen-like, BCG and the pathogenic M. bovis indifferent mouse, human and bovine macrophages. The bacteriocidal effects of RNI wererestricted for all bacterial species to the early stages of infection. EM analysis showedclearly that all the mycobacteria remained within phagosomes even at late times ofinfection. The fraction of BCG and M. bovis found in mature phagolysosomes rarelyexceeded 10 % of total, irrespective of whether bacteria were growing, latent or beingkilled, with little correlation between the extent of phagosome maturation and thedegree of killing. Theoretical modelling of our data identified two different potentialsets of explanations that are consistent with our results. The model we favour is one inwhich a small but significant fraction of BCG is killed in an early phagosome, thenmaturation of a small fraction of phagosomes with both live and killed bacteria,followed by extremely rapid killing and digestion of the bacteria in phago-lysosomes.Fil: Jordao, Luisa. Universidad de Lisboa. Facultad de Farmacia; PortugalFil: Bleck, Christopher K.. European Molecular Biology Laboratory; AlemaniaFil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. European Molecular Biology Laboratory; AlemaniaFil: Griffiths, Gareth. European Molecular Biology Laboratory; AlemaniaFil: Anes, Elsa. Universidad de Lisboa. Facultad de Farmacia; PortugalWiley Blackwell Publishing, Inc2008-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/127532Jordao, Luisa; Bleck, Christopher K.; Mayorga, Luis Segundo; Griffiths, Gareth; Anes, Elsa; On the killing of mycobacteria by macrophages; Wiley Blackwell Publishing, Inc; Cellular Microbiology (print); 10; 2; 2-2008; 529-5481462-5814CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/toc/14625822/2008/10/2info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1462-5822.2007.01067.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:58:52Zoai:ri.conicet.gov.ar:11336/127532instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:58:52.895CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv On the killing of mycobacteria by macrophages
title On the killing of mycobacteria by macrophages
spellingShingle On the killing of mycobacteria by macrophages
Jordao, Luisa
Mathematical model
Macrophage
Mycobacterium
Phagosome
title_short On the killing of mycobacteria by macrophages
title_full On the killing of mycobacteria by macrophages
title_fullStr On the killing of mycobacteria by macrophages
title_full_unstemmed On the killing of mycobacteria by macrophages
title_sort On the killing of mycobacteria by macrophages
dc.creator.none.fl_str_mv Jordao, Luisa
Bleck, Christopher K.
Mayorga, Luis Segundo
Griffiths, Gareth
Anes, Elsa
author Jordao, Luisa
author_facet Jordao, Luisa
Bleck, Christopher K.
Mayorga, Luis Segundo
Griffiths, Gareth
Anes, Elsa
author_role author
author2 Bleck, Christopher K.
Mayorga, Luis Segundo
Griffiths, Gareth
Anes, Elsa
author2_role author
author
author
author
dc.subject.none.fl_str_mv Mathematical model
Macrophage
Mycobacterium
Phagosome
topic Mathematical model
Macrophage
Mycobacterium
Phagosome
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Both pathogenic and non-pathogenic mycobacteria are internalized into macrophagephagosomes. Whereas the non-pathogenic types are invariably killed by allmacrophages, the pathogens generally survive and grow. Here, we addressed thesurvival, production of nitrogen intermediates (RNI) and intracellular trafficking of thenon-pathogenic M. smegmatis, the pathogen-like, BCG and the pathogenic M. bovis indifferent mouse, human and bovine macrophages. The bacteriocidal effects of RNI wererestricted for all bacterial species to the early stages of infection. EM analysis showedclearly that all the mycobacteria remained within phagosomes even at late times ofinfection. The fraction of BCG and M. bovis found in mature phagolysosomes rarelyexceeded 10 % of total, irrespective of whether bacteria were growing, latent or beingkilled, with little correlation between the extent of phagosome maturation and thedegree of killing. Theoretical modelling of our data identified two different potentialsets of explanations that are consistent with our results. The model we favour is one inwhich a small but significant fraction of BCG is killed in an early phagosome, thenmaturation of a small fraction of phagosomes with both live and killed bacteria,followed by extremely rapid killing and digestion of the bacteria in phago-lysosomes.
Fil: Jordao, Luisa. Universidad de Lisboa. Facultad de Farmacia; Portugal
Fil: Bleck, Christopher K.. European Molecular Biology Laboratory; Alemania
Fil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. European Molecular Biology Laboratory; Alemania
Fil: Griffiths, Gareth. European Molecular Biology Laboratory; Alemania
Fil: Anes, Elsa. Universidad de Lisboa. Facultad de Farmacia; Portugal
description Both pathogenic and non-pathogenic mycobacteria are internalized into macrophagephagosomes. Whereas the non-pathogenic types are invariably killed by allmacrophages, the pathogens generally survive and grow. Here, we addressed thesurvival, production of nitrogen intermediates (RNI) and intracellular trafficking of thenon-pathogenic M. smegmatis, the pathogen-like, BCG and the pathogenic M. bovis indifferent mouse, human and bovine macrophages. The bacteriocidal effects of RNI wererestricted for all bacterial species to the early stages of infection. EM analysis showedclearly that all the mycobacteria remained within phagosomes even at late times ofinfection. The fraction of BCG and M. bovis found in mature phagolysosomes rarelyexceeded 10 % of total, irrespective of whether bacteria were growing, latent or beingkilled, with little correlation between the extent of phagosome maturation and thedegree of killing. Theoretical modelling of our data identified two different potentialsets of explanations that are consistent with our results. The model we favour is one inwhich a small but significant fraction of BCG is killed in an early phagosome, thenmaturation of a small fraction of phagosomes with both live and killed bacteria,followed by extremely rapid killing and digestion of the bacteria in phago-lysosomes.
publishDate 2008
dc.date.none.fl_str_mv 2008-02
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/11336/127532
Jordao, Luisa; Bleck, Christopher K.; Mayorga, Luis Segundo; Griffiths, Gareth; Anes, Elsa; On the killing of mycobacteria by macrophages; Wiley Blackwell Publishing, Inc; Cellular Microbiology (print); 10; 2; 2-2008; 529-548
1462-5814
CONICET Digital
CONICET
url http://hdl.handle.net/11336/127532
identifier_str_mv Jordao, Luisa; Bleck, Christopher K.; Mayorga, Luis Segundo; Griffiths, Gareth; Anes, Elsa; On the killing of mycobacteria by macrophages; Wiley Blackwell Publishing, Inc; Cellular Microbiology (print); 10; 2; 2-2008; 529-548
1462-5814
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://onlinelibrary.wiley.com/toc/14625822/2008/10/2
info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1462-5822.2007.01067.x
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
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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_ 1844613751133700096
score 13.070432

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