| Literature DB >> 12637671 |
Capucine Picard1, Anne Puel, Marion Bonnet, Cheng-Lung Ku, Jacinta Bustamante, Kun Yang, Claire Soudais, Stéphanie Dupuis, Jacqueline Feinberg, Claire Fieschi, Carole Elbim, Remi Hitchcock, David Lammas, Graham Davies, Abdulaziz Al-Ghonaium, Hassan Al-Rayes, Sulaiman Al-Jumaah, Sami Al-Hajjar, Ibrahim Zaid Al-Mohsen, Husn H Frayha, Rajivi Rucker, Thomas R Hawn, Alan Aderem, Haysam Tufenkeji, Soichi Haraguchi, Noorbibi K Day, Robert A Good, Marie-Anne Gougerot-Pocidalo, Adrian Ozinsky, Jean-Laurent Casanova.
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.Entities:
Mesh：
Substances：
Year: 2003 PMID： 12637671 DOI： 10.1126/science.1081902
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728