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Critical role for Ipaf in Pseudomonas aeruginosa -induced caspase-1 activation

dc.contributor.authorFranchi, Luigien_US
dc.contributor.authorStoolman, Joshua S.en_US
dc.contributor.authorKanneganti, Thirumala-Devien_US
dc.contributor.authorVerma, Amrishaen_US
dc.contributor.authorRamphal, Reubenen_US
dc.date.accessioned2007-12-04T18:25:42Z
dc.date.available2008-11-05T15:05:43Zen_US
dc.date.issued2007-11en_US
dc.identifier.citationFranchi, Luigi; Stoolman, Joshua; Kanneganti, Thirumala-Devi; Verma, Amrisha; Ramphal, Reuben (2007). "Critical role for Ipaf in Pseudomonas aeruginosa -induced caspase-1 activation." European Journal of Immunology 37(11): 3030-3039. <http://hdl.handle.net/2027.42/57332>en_US
dc.identifier.issn0014-2980en_US
dc.identifier.issn1521-4141en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/57332
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17935074&dopt=citation
dc.description.abstractPseudomonas aeruginosa is an opportunistic Gram-negative human pathogen that is responsible for a broad range of infections in individuals with a variety of predisposing conditions. After infection, P. aeruginosa induces a marked inflammatory response in the host. However the mechanisms involved in bacterium recognition and induction of immune responses are poorly understood. Here we report that the Nod-like receptor family member Ipaf is required for optimal bacterial clearance in an in vivo model of P. aeruginosa lung infection. Further analysis showed that bacterial flagellin was essential for caspase-1 and IL-1β and this activity depended on Ipaf and the adaptor ASC but not TLR5. Notably, P. aeruginosa induced macrophage cell death and this event relied on flagellin and Ipaf but not on ASC. Analysis of Pseudomonas mutants revealed that different amino acid residues of flagellin were critical for sensing by Ipaf and TLR5. Finally, activation of caspase-1 and IL-1β secretion by P. aeruginosa required a functional type III secretion system, but not the effector molecules ExoS, ExoT and ExoY. These results provide new insight into the interaction of P. aeruginosa with host macrophages and suggest that distinct regions of flagellin are sensed by Ipaf and TLR5.en_US
dc.format.extent367974 bytes
dc.format.extent3118 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.publisherWILEY-VCH Verlagen_US
dc.subject.otherLife and Medical Sciencesen_US
dc.subject.otherMicrobiology and Immunologyen_US
dc.titleCritical role for Ipaf in Pseudomonas aeruginosa -induced caspase-1 activationen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelBiological Chemistryen_US
dc.subject.hlbsecondlevelPublic Healthen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.subject.hlbtoplevelScienceen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, USAen_US
dc.contributor.affiliationumDepartment of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, USAen_US
dc.contributor.affiliationumDepartment of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, USAen_US
dc.contributor.affiliationotherDepartment of Medicine, University of Florida, Gainesville, USAen_US
dc.contributor.affiliationotherDepartment of Medicine, University of Florida, Gainesville, USAen_US
dc.identifier.pmid17935074
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/57332/1/3030_ftp.pdfen_US
dc.identifier.doihttp://dx.doi.org/10.1002/eji.200737532en_US
dc.identifier.sourceEuropean Journal of Immunologyen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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