2024-03-29T14:36:27Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/507882016-09-02T11:32:58Zcom_10261_118com_10261_6col_10261_371
Regueiro, Verónica
Moranta, David
Frank, Christian G.
Larrarte, Eider
Margareto, Javier
March, Catalina
Garmendia, Juncal
Bengoechea, José Antonio
2012-06-05T09:41:46Z
2012-06-05T09:41:46Z
2011
Cellular Microbiology 13(1): 135-153 (2011)
http://hdl.handle.net/10261/50788
10.1111/j.1462-5822.2010.01526.x
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 pro-inflammatory mediators-induced IL-8 secretion. Klebsiella antagonizes the activation of NF-κB 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-κB 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-1β-induced IL-8 secretion. A capsule (CPS) mutant does not attenuate the inflammatory response. However, purified CPS neither reduces IL-1β-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. © 2010 Blackwell Publishing Ltd.
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Klebsiella pneumoniae subverts the activation of inflammatory responses in a NOD1-dependent manner
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