Inhibition of inflammasome activation by a clinical strain of Klebsiella pneumoniae impairs efferocytosis and leads to bacterial dissemination

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dc.contributor.authorCodo, Ana Campos [UNESP]
dc.contributor.authorSaraiva, Amanda Correia [UNESP]
dc.contributor.authorSantos, Leonardo Lima dos
dc.contributor.authorVisconde, Marina Francisco
dc.contributor.authorGales, Ana Cristina
dc.contributor.authorZamboni, Dario Simoes
dc.contributor.authorMedeiros, Alexandra Ivo [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2019-10-04T12:33:23Z
dc.date.available2019-10-04T12:33:23Z
dc.date.issued2018-12-05
dc.description.abstractKlebsiella pneumoniae is a Gram-negative bacterium responsible for severe cases of nosocomial pneumonia. During the infectious process, both neutrophils and monocytes migrate to the site of infection, where they carry out their effector functions and can be affected by different patterns of cell death. Our data show that clinical strains of K. pneumoniae have dissimilar mechanisms for surviving within macrophages; these mechanisms include modulation of microbicidal mediators and cell death. The A28006 strain induced high IL-1 beta production and pyroptotic cell death in macrophages; by contrast, the A54970 strain induced high IL-10 production and low IL-1 beta production by macrophages. Pyroptotic cell death induced by the A28006 strain leads to a significant increase in bacterial sensitivity to hydrogen peroxide, and efferocytosis of the pyroptotic cells results in efficient bacterial clearance both in vitro and in vivo. In addition, the A54970 strain was able to inhibit inflammasome activation and pyroptotic cell death by inducing IL-10 production. Here, for the first time, we present a K. pneumoniae strain able to inhibit inflammasome activation, leading to bacterial survival and dissemination in the host. The understanding of possible escape mechanisms is essential in the search for alternative treatments against multidrug-resistant bacteria.en
dc.description.affiliationSao Paulo State Univ, Sch Pharmaceut Sci, Dept Biol Sci, Araraquara, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Sch Med, Dept Cell & Mol Biol & Pathogen Bioagents, Ribeirao Preto, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Internal Med, Escola Paulista Med, Div Infect Dis, Sao Paulo, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Sch Pharmaceut Sci, Dept Biol Sci, Araraquara, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdFAPESP: 2011/17611-7
dc.description.sponsorshipIdFAPESP: 2013/18039-0
dc.description.sponsorshipIdFAPESP: 2017/19870-6
dc.description.sponsorshipIdFAPESP: 2017/19265-5
dc.description.sponsorshipIdCNPq: 302097/2010-4
dc.description.sponsorshipIdCNPq: 471945/2012-9
dc.description.sponsorshipIdCNPq: 305535/2014-5
dc.description.sponsorshipIdCNPq: 116820/2016-0
dc.description.sponsorshipIdCNPq: 159637/2017-1
dc.description.sponsorshipId: PROPG/UNESP - 05/2018
dc.format.extent14
dc.identifierhttp://dx.doi.org/10.1038/s41419-018-1214-5
dc.identifier.citationCell Death & Disease. London: Nature Publishing Group, v. 9, 14 p., 2018.
dc.identifier.doi10.1038/s41419-018-1214-5
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/11449/185181
dc.identifier.wosWOS:000452323500018
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofCell Death & Disease
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.titleInhibition of inflammasome activation by a clinical strain of Klebsiella pneumoniae impairs efferocytosis and leads to bacterial disseminationen
dc.typeArtigo
dcterms.rightsHolderNature Publishing Group
unesp.author.lattes8756770929017974[7]
unesp.author.orcid0000-0001-9036-5772[1]
unesp.author.orcid0000-0001-6048-3647[7]

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