Efferocytosis is an innate antibacterial mechanism

Detalhes bibliográficos
Autor(a) principal: Martin, Constance J.
Data de Publicação: 2012
Outros Autores: Booty, Matthew G., Rosebrock, Tracy R., Nunes-Alves, Cláudio, Desjardins, Danielle M., Keren, Iris, Fortune, Sarah M., Remold, Heinz G., Behar, Samuel M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/67425
Resumo: Mycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. Although apoptosis of M. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved. We find that after apoptosis, M. tuberculosis-infected macrophages are rapidly taken up by uninfected macrophages through efferocytosis, a dedicated apoptotic cell engulfment process. Efferocytosis of M. tuberculosis sequestered within an apoptotic macrophage further compartmentalizes the bacterium and delivers it along with the apoptotic cell debris to the lysosomal compartment. M. tuberculosis is killed only after efferocytosis, indicating that apoptosis itself is not intrinsically bactericidal but requires subsequent phagocytic uptake and lysosomal fusion of the apoptotic body harboring the bacterium. While efferocytosis is recognized as a constitutive housekeeping function of macrophages, these data indicate that it can also function as an antimicrobial effector mechanism.
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spelling Efferocytosis is an innate antibacterial mechanismAnimalsCells, CulturedImmune EvasionLysosomesMacrophagesMiceMice, Inbred C57BLMicrobial ViabilityMicroscopy, Electron, TransmissionMicroscopy, FluorescenceMycobacterium tuberculosisApoptosisPhagocytosisCiências Médicas::Medicina BásicaScience & TechnologyMycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. Although apoptosis of M. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved. We find that after apoptosis, M. tuberculosis-infected macrophages are rapidly taken up by uninfected macrophages through efferocytosis, a dedicated apoptotic cell engulfment process. Efferocytosis of M. tuberculosis sequestered within an apoptotic macrophage further compartmentalizes the bacterium and delivers it along with the apoptotic cell debris to the lysosomal compartment. M. tuberculosis is killed only after efferocytosis, indicating that apoptosis itself is not intrinsically bactericidal but requires subsequent phagocytic uptake and lysosomal fusion of the apoptotic body harboring the bacterium. While efferocytosis is recognized as a constitutive housekeeping function of macrophages, these data indicate that it can also function as an antimicrobial effector mechanism.Behar, Fortune, and Remold labs for reagents, helpful discussion, and insights. TIM4-blocking antibodies were a generous gift of Vijay Kuchroo. Members of the Harvard Electron Microscopy Core Facility helped in the preparation, staining, and operation of the electron microscope. The Small Animal Biocontainment (ABC) Suite is supported by CFAR 5P30AI060354. T.R.R and S.M.F were supported by CFAR 5P30AI060354, DP2-0d001378, and T32-AI07387. C.N.A. is the recipient of a fellowship from FCT. S.M.B and H.G.R. were supported by R56AI084161 and R01AI072143.Cell PressUniversidade do MinhoMartin, Constance J.Booty, Matthew G.Rosebrock, Tracy R.Nunes-Alves, CláudioDesjardins, Danielle M.Keren, IrisFortune, Sarah M.Remold, Heinz G.Behar, Samuel M.2012-09-132012-09-13T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/67425engMartin, C. J., Booty, M. G., Rosebrock, T. R., Nunes-Alves, C., Desjardins, D. M., et. al.(2012). Efferocytosis is an innate antibacterial mechanism. Cell host & microbe, 12(3), 289-3001931-31281934-606910.1016/j.chom.2012.06.01022980326https://www.sciencedirect.com/science/article/pii/S1931312812002429info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:18:09Zoai:repositorium.sdum.uminho.pt:1822/67425Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:10:53.900507Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Efferocytosis is an innate antibacterial mechanism
title Efferocytosis is an innate antibacterial mechanism
spellingShingle Efferocytosis is an innate antibacterial mechanism
Martin, Constance J.
Animals
Cells, Cultured
Immune Evasion
Lysosomes
Macrophages
Mice
Mice, Inbred C57BL
Microbial Viability
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Mycobacterium tuberculosis
Apoptosis
Phagocytosis
Ciências Médicas::Medicina Básica
Science & Technology
title_short Efferocytosis is an innate antibacterial mechanism
title_full Efferocytosis is an innate antibacterial mechanism
title_fullStr Efferocytosis is an innate antibacterial mechanism
title_full_unstemmed Efferocytosis is an innate antibacterial mechanism
title_sort Efferocytosis is an innate antibacterial mechanism
author Martin, Constance J.
author_facet Martin, Constance J.
Booty, Matthew G.
Rosebrock, Tracy R.
Nunes-Alves, Cláudio
Desjardins, Danielle M.
Keren, Iris
Fortune, Sarah M.
Remold, Heinz G.
Behar, Samuel M.
author_role author
author2 Booty, Matthew G.
Rosebrock, Tracy R.
Nunes-Alves, Cláudio
Desjardins, Danielle M.
Keren, Iris
Fortune, Sarah M.
Remold, Heinz G.
Behar, Samuel M.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Martin, Constance J.
Booty, Matthew G.
Rosebrock, Tracy R.
Nunes-Alves, Cláudio
Desjardins, Danielle M.
Keren, Iris
Fortune, Sarah M.
Remold, Heinz G.
Behar, Samuel M.
dc.subject.por.fl_str_mv Animals
Cells, Cultured
Immune Evasion
Lysosomes
Macrophages
Mice
Mice, Inbred C57BL
Microbial Viability
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Mycobacterium tuberculosis
Apoptosis
Phagocytosis
Ciências Médicas::Medicina Básica
Science & Technology
topic Animals
Cells, Cultured
Immune Evasion
Lysosomes
Macrophages
Mice
Mice, Inbred C57BL
Microbial Viability
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Mycobacterium tuberculosis
Apoptosis
Phagocytosis
Ciências Médicas::Medicina Básica
Science & Technology
description Mycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. Although apoptosis of M. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved. We find that after apoptosis, M. tuberculosis-infected macrophages are rapidly taken up by uninfected macrophages through efferocytosis, a dedicated apoptotic cell engulfment process. Efferocytosis of M. tuberculosis sequestered within an apoptotic macrophage further compartmentalizes the bacterium and delivers it along with the apoptotic cell debris to the lysosomal compartment. M. tuberculosis is killed only after efferocytosis, indicating that apoptosis itself is not intrinsically bactericidal but requires subsequent phagocytic uptake and lysosomal fusion of the apoptotic body harboring the bacterium. While efferocytosis is recognized as a constitutive housekeeping function of macrophages, these data indicate that it can also function as an antimicrobial effector mechanism.
publishDate 2012
dc.date.none.fl_str_mv 2012-09-13
2012-09-13T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/67425
url http://hdl.handle.net/1822/67425
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Martin, C. J., Booty, M. G., Rosebrock, T. R., Nunes-Alves, C., Desjardins, D. M., et. al.(2012). Efferocytosis is an innate antibacterial mechanism. Cell host & microbe, 12(3), 289-300
1931-3128
1934-6069
10.1016/j.chom.2012.06.010
22980326
https://www.sciencedirect.com/science/article/pii/S1931312812002429
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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