Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
dARK ID: | ark:/48912/001300000v0j5 |
Texto Completo: | http://dx.doi.org/10.1186/1471-2180-14-128 http://repositorio.unifesp.br/handle/11600/37773 |
Resumo: | Background: Phospholipases C (PLCs) are virulence factors found in several bacteria. in Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on macrophages, but the mechanisms involved in PLC-induced cell death are not fully understood. It has been reported that induction of cell necrosis by virulent Mtb is coordinated by subversion of PGE(2), an essential factor in cell membrane protection.Results: Using two Mtb clinical isolates carrying genetic variations in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes, is more resistant to alveolar macrophage microbicidal activity than the isolate 97-1200, which has all PLC genes deleted. the isolate 97-1505 also induced higher rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression and PGE(2) production. To address the direct effect of mycobacterial PLC on cell necrosis and PGE(2) inhibition, both isolates were treated with PLC inhibitors prior to macrophage infection. Interestingly, inhibition of PLCs affected the ability of the isolate 97-1505 to induce necrosis, leading to cell death rates similar to those induced by the isolate 97-1200. Finally, PGE(2) production by Mtb 97-1505-infected macrophages was restored to levels similar to those produced by 97-1200-infected cells.Conclusions: Mycobacterium tuberculosis bearing PLCs genes induces alveolar macrophage necrosis, which is associated to subversion of PGE(2) production. |
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Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophagesMycobacteriumLipid mediatorPhospholipase CCell deathMacrophage necrosisProstaglandinsBackground: Phospholipases C (PLCs) are virulence factors found in several bacteria. in Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on macrophages, but the mechanisms involved in PLC-induced cell death are not fully understood. It has been reported that induction of cell necrosis by virulent Mtb is coordinated by subversion of PGE(2), an essential factor in cell membrane protection.Results: Using two Mtb clinical isolates carrying genetic variations in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes, is more resistant to alveolar macrophage microbicidal activity than the isolate 97-1200, which has all PLC genes deleted. the isolate 97-1505 also induced higher rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression and PGE(2) production. To address the direct effect of mycobacterial PLC on cell necrosis and PGE(2) inhibition, both isolates were treated with PLC inhibitors prior to macrophage infection. Interestingly, inhibition of PLCs affected the ability of the isolate 97-1505 to induce necrosis, leading to cell death rates similar to those induced by the isolate 97-1200. Finally, PGE(2) production by Mtb 97-1505-infected macrophages was restored to levels similar to those produced by 97-1200-infected cells.Conclusions: Mycobacterium tuberculosis bearing PLCs genes induces alveolar macrophage necrosis, which is associated to subversion of PGE(2) production.Univ São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniv São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Bioquim & Imunol, BR-14040903 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 2009/07169-5FAPESP: 2011/01845-9Biomed Central LtdUniversidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)Assis, Patricia A.Espindola, Milena S.Paula-Silva, Francisco W. G.Rios, Wendy M.Pereira, Priscilla A. T.Leao, Sylvia Cardoso [UNIFESP]Silva, Celio L.Faccioli, Lucia H.2016-01-24T14:37:18Z2016-01-24T14:37:18Z2014-05-19info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10application/pdfhttp://dx.doi.org/10.1186/1471-2180-14-128Bmc Microbiology. London: Biomed Central Ltd, v. 14, 10 p., 2014.10.1186/1471-2180-14-128WOS000338156500001.pdf1471-2180http://repositorio.unifesp.br/handle/11600/37773WOS:000338156500001ark:/48912/001300000v0j5engBmc Microbiologyinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-08T09:15:51Zoai:repositorio.unifesp.br/:11600/37773Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:38:29.509057Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages |
title |
Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages |
spellingShingle |
Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages Assis, Patricia A. Mycobacterium Lipid mediator Phospholipase C Cell death Macrophage necrosis Prostaglandins |
title_short |
Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages |
title_full |
Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages |
title_fullStr |
Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages |
title_full_unstemmed |
Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages |
title_sort |
Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages |
author |
Assis, Patricia A. |
author_facet |
Assis, Patricia A. Espindola, Milena S. Paula-Silva, Francisco W. G. Rios, Wendy M. Pereira, Priscilla A. T. Leao, Sylvia Cardoso [UNIFESP] Silva, Celio L. Faccioli, Lucia H. |
author_role |
author |
author2 |
Espindola, Milena S. Paula-Silva, Francisco W. G. Rios, Wendy M. Pereira, Priscilla A. T. Leao, Sylvia Cardoso [UNIFESP] Silva, Celio L. Faccioli, Lucia H. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Assis, Patricia A. Espindola, Milena S. Paula-Silva, Francisco W. G. Rios, Wendy M. Pereira, Priscilla A. T. Leao, Sylvia Cardoso [UNIFESP] Silva, Celio L. Faccioli, Lucia H. |
dc.subject.por.fl_str_mv |
Mycobacterium Lipid mediator Phospholipase C Cell death Macrophage necrosis Prostaglandins |
topic |
Mycobacterium Lipid mediator Phospholipase C Cell death Macrophage necrosis Prostaglandins |
description |
Background: Phospholipases C (PLCs) are virulence factors found in several bacteria. in Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on macrophages, but the mechanisms involved in PLC-induced cell death are not fully understood. It has been reported that induction of cell necrosis by virulent Mtb is coordinated by subversion of PGE(2), an essential factor in cell membrane protection.Results: Using two Mtb clinical isolates carrying genetic variations in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes, is more resistant to alveolar macrophage microbicidal activity than the isolate 97-1200, which has all PLC genes deleted. the isolate 97-1505 also induced higher rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression and PGE(2) production. To address the direct effect of mycobacterial PLC on cell necrosis and PGE(2) inhibition, both isolates were treated with PLC inhibitors prior to macrophage infection. Interestingly, inhibition of PLCs affected the ability of the isolate 97-1505 to induce necrosis, leading to cell death rates similar to those induced by the isolate 97-1200. Finally, PGE(2) production by Mtb 97-1505-infected macrophages was restored to levels similar to those produced by 97-1200-infected cells.Conclusions: Mycobacterium tuberculosis bearing PLCs genes induces alveolar macrophage necrosis, which is associated to subversion of PGE(2) production. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-05-19 2016-01-24T14:37:18Z 2016-01-24T14:37:18Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1186/1471-2180-14-128 Bmc Microbiology. London: Biomed Central Ltd, v. 14, 10 p., 2014. 10.1186/1471-2180-14-128 WOS000338156500001.pdf 1471-2180 http://repositorio.unifesp.br/handle/11600/37773 WOS:000338156500001 |
dc.identifier.dark.fl_str_mv |
ark:/48912/001300000v0j5 |
url |
http://dx.doi.org/10.1186/1471-2180-14-128 http://repositorio.unifesp.br/handle/11600/37773 |
identifier_str_mv |
Bmc Microbiology. London: Biomed Central Ltd, v. 14, 10 p., 2014. 10.1186/1471-2180-14-128 WOS000338156500001.pdf 1471-2180 WOS:000338156500001 ark:/48912/001300000v0j5 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bmc Microbiology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
10 application/pdf |
dc.publisher.none.fl_str_mv |
Biomed Central Ltd |
publisher.none.fl_str_mv |
Biomed Central Ltd |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
_version_ |
1818602520362090496 |