| http://purl.uniprot.org/citations/17878374 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17878374 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17878374 | http://www.w3.org/2000/01/rdf-schema#comment | "Polymorphonuclear neutrophils (PMN) play a key role in innate immunity. Their activation and survival are tightly regulated by microbial products via pattern recognition receptors such as TLRs, which mediate recruitment of the IL-1R-associated kinase (IRAK) complex. We describe a new inherited IRAK-4 deficiency in a child with recurrent pyogenic bacterial infections. Analysis of the IRAK4 gene showed compound heterozygosity with two mutations: a missense mutation in the death domain of the protein (pArg12Cys) associated in cis-with a predicted benign variant (pArg391His); and a splice site mutation in intron 7 that led to the skipping of exon 7. A nontruncated IRAK-4 protein was detected by Western blotting. The patient's functional deficiency of IRAK-4 protein was confirmed by the absence of IRAK-1 phosphorylation after stimulation with all TLR agonists tested. The patient's PMNs showed strongly impaired responses (L-selectin and CD11b expression, oxidative burst, cytokine production, cell survival) to TLR agonists which engage TLR1/2, TLR2/6, TLR4, and TLR7/8; in contrast, the patient's PMN responses to CpG-DNA (TLR9) were normal, except for cytokine production. The surprisingly normal effect of CpG-DNA on PMN functions and apoptosis disappeared after pretreatment with PI3K inhibitors. Together, these results suggest the existence of an IRAK-4-independent TLR9-induced transduction pathway leading to PI3K activation. This alternative pathway may play a key role in PMN control of infections by microorganisms other than pyogenic bacteria in inherited IRAK-4 deficiency."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.179.7.4754"xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.179.7.4754"xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Henry D."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Henry D."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Lacapere J.J."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Lacapere J.J."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Gerard B."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Gerard B."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Grandchamp B."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Grandchamp B."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Dang P.M."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Dang P.M."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "El Benna J."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "El Benna J."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Gougerot-Pocidalo M.A."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Gougerot-Pocidalo M.A."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Francois S."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Francois S."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Elbim C."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Elbim C."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Hoarau C."xsd:string |
| http://purl.uniprot.org/citations/17878374 | http://purl.uniprot.org/core/author | "Hoarau C."xsd:string |