Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages

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dc.contributor.authorAssis, Patricia A.
dc.contributor.authorEspindola, Milena S.
dc.contributor.authorPaula-Silva, Francisco W. G.
dc.contributor.authorRios, Wendy M.
dc.contributor.authorPereira, Priscilla A. T.
dc.contributor.authorLeao, Sylvia Cardoso [UNIFESP]
dc.contributor.authorSilva, Celio L.
dc.contributor.authorFaccioli, Lucia H.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:37:18Z
dc.date.available2016-01-24T14:37:18Z
dc.date.issued2014-05-19
dc.description.abstractBackground: 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.en
dc.description.affiliationUniv São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, SP, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Bioquim & Imunol, BR-14040903 Ribeirao Preto, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDFAPESP: 2009/07169-5
dc.description.sponsorshipIDFAPESP: 2011/01845-9
dc.format.extent10
dc.identifierhttp://dx.doi.org/10.1186/1471-2180-14-128
dc.identifier.citationBmc Microbiology. London: Biomed Central Ltd, v. 14, 10 p., 2014.
dc.identifier.doi10.1186/1471-2180-14-128
dc.identifier.fileWOS000338156500001.pdf
dc.identifier.issn1471-2180
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/37773
dc.identifier.wosWOS:000338156500001
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofBmc Microbiology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectMycobacteriumen
dc.subjectLipid mediatoren
dc.subjectPhospholipase Cen
dc.subjectCell deathen
dc.subjectMacrophage necrosisen
dc.subjectProstaglandinsen
dc.titleMycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophagesen
dc.typeinfo:eu-repo/semantics/article
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