Efferocytosis is an innate antibacterial mechanism
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , , , , , , |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132539363786752 |