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Pyogenic bacterial infections in humans with IRAK-4 deficiency.
| Title | Pyogenic bacterial infections in humans with IRAK-4 deficiency. |
| Publication Type | Journal Article |
| Year of Publication | 2003 |
| Authors | Picard, C, Puel, A, Bonnet, M, Ku, C-L, Bustamante, J, Yang, K, Soudais, C, Dupuis, S, Feinberg, J, Fieschi, C, Elbim, C, Hitchcock, R, Lammas, D, Davies, G, Al-Ghonaium, A, Al-Rayes, H, Al-Jumaah, S, Al-Hajjar, S, Al-Mohsen, IZaid, Frayha, HH, Rucker, R, Hawn, TR, Aderem, A, Tufenkeji, H, Haraguchi, S, Day, NK, Good, RA, Gougerot-Pocidalo, M-A, Ozinsky, A, Casanova, J-L |
| Journal | Science |
| Volume | 299 |
| Issue | 5615 |
| Pagination | 2076-9 |
| Date Published | 2003 Mar 28 |
| ISSN | 1095-9203 |
| Keywords | Alleles, Child, Codon, Terminator, Cytokines, Drosophila Proteins, Female, Fibroblasts, Humans, Interleukin-1 Receptor-Associated Kinases, Interleukins, Lipopolysaccharides, Male, Membrane Glycoproteins, Monocytes, Mutation, Neutrophils, Pedigree, Phosphotransferases (Alcohol Group Acceptor), Pneumococcal Infections, Protein Structure, Tertiary, Receptors, Cell Surface, Receptors, Interleukin, Receptors, Interleukin-1, Signal Transduction, Staphylococcal Infections, Toll-Like Receptors, Tumor Necrosis Factor-alpha |
| Abstract | Members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily share an intracytoplasmic Toll-IL-1 receptor (TIR) domain, which mediates recruitment of the interleukin-1 receptor-associated kinase (IRAK) complex via TIR-containing adapter molecules. We describe three unrelated children with inherited IRAK-4 deficiency. Their blood and fibroblast cells did not activate nuclear factor kappaB and mitogen-activated protein kinase (MAPK) and failed to induce downstream cytokines in response to any of the known ligands of TIR-bearing receptors. The otherwise healthy children developed infections caused by pyogenic bacteria. These findings suggest that, in humans, the TIR-IRAK signaling pathway is crucial for protective immunity against specific bacteria but is redundant against most other microorganisms. |
| DOI | 10.1126/science.1081902 |
| Alternate Journal | Science |
| PubMed ID | 12637671 |
