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Klebsiella pneumoniae subverts the activation of inflammatory responses in a NOD1-dependent manner.

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dc.contributor.author Regueiro, Verónica
dc.contributor.author Moranta Mesquida, David
dc.contributor.author Frank, Christian G.
dc.contributor.author Larrarte, Eider
dc.contributor.author Margareto, Javier
dc.contributor.author March, Catalina
dc.contributor.author Garmendia, Junkal
dc.contributor.author Bengoechea, José Antonio
dc.date.accessioned 2018-09-17T08:19:16Z
dc.identifier.uri http://hdl.handle.net/11201/147435
dc.description.abstract [eng] Klebsiella pneumoniae is an important cause of community-acquired and nosocomial pneumonia. Subversion of inflammation is essential for pathogen survival during infection. Evidence indicates that K. pneumoniae infections are characterized by lacking an early inflammatory response although the molecular bases are currently unknown. Here we unveil a novel strategy employed by a pathogen to counteract the activation of inflammatory responses. K. pneumoniae attenuates proinflammatory mediators-induced IL-8 secretion. Klebsiella antagonizes the activation of NF-kB via the deubiquitinase CYLD and blocks the phosphorylation of mitogen-activated protein kinases (MAPKs) via the MAPK phosphatase MKP-1. Our studies demonstrate that K. pneumoniae has evolved the capacity to manipulate host systems dedicated to control the immune balance. To exert this anti-inflammatory effect, Klebsiella engages NOD1. In NOD1 knock-down cells, Klebsiella neither induces the expression of CYLD and MKP-1 nor blocks the activation of NF-kB and MAPKs. Klebsiella inhibits Rac1 activation; and inhibition of Rac1 activity triggers a NOD1-mediated CYLD and MKP-1 expression which in turn attenuates IL-1b-induced IL-8 secretion. A capsule (CPS) mutant does not attenuate the inflammatory response. However, purified CPS neither reduces IL-1b-induced IL-8 secretion nor induces the expression of CYLD and MKP-1 thereby indicating that CPS is necessary but not sufficient to attenuate inflammation.
dc.format application/pdf
dc.relation.isformatof Versió postprint del document publicat a: https://doi.org/10.1111/j.1462-5822.2010.01526.x
dc.relation.ispartof Cellular Microbiology, 2010, vol. 13, num. 1, p. 135-153
dc.rights (c) John Wiley & Sons, Ltd, 2010
dc.subject.classification 576 - Biologia cel·lular i subcel·lular. Citologia
dc.subject.other 576 - Cellular and subcellular biology. Cytology
dc.title Klebsiella pneumoniae subverts the activation of inflammatory responses in a NOD1-dependent manner.
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion
dc.date.updated 2018-09-17T08:19:16Z
dc.date.embargoEndDate info:eu-repo/date/embargoEnd/2075-01-01
dc.embargo 2075-01-01
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess
dc.identifier.doi https://doi.org/10.1111/j.1462-5822.2010.01526.x


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