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- Title
Pyogenic bacterial infections in humans with IRAK-4 deficiency.
- Authors
Picard, Capucine; Puel, Anne; Bonnet, Marion; Ku, Cheng-Lung; Bustamante, Jacinta; Yang, Kun; Soudais, Claire; Dupuis, Stéphanie; Feinberg, Jacqueline; Fieschi, Claire; Elbim, Carole; Hitchcock, Remi; Lammas, David; Davies, Graham; Al-Ghonaium, Abdulaziz; Al-Rayes, Hassan; Al-Jumaah, Sulaiman; Al-Hajjar, Sami; Al-Mohsen, Ibrahim Zaid; Frayha, Husn H; Rucker, Rajivi; Hawn, Thomas R; Aderem, Alan; Tufenkeji, Haysam; Haraguchi, Soichi; Day, Noorbibi K; Good, Robert A; Gougerot-Pocidalo, Marie-Anne; Ozinsky, Adrian; Casanova, Jean-Laurent
- 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.
- Publication
Science (New York, N.Y.), 2003, Vol 299, Issue 5615, p2076
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1081902