1. Pyogenic Bacterial Infections in Humans with IRAK-4 Deficiency
- Author
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Capucine Picard, 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, and Jean-Laurent Casanova
- Subjects
Lipopolysaccharides ,Male ,Neutrophils ,Receptors, Cell Surface ,Monocytes ,Pneumococcal Infections ,Drosophila Proteins ,Humans ,Child ,Alleles ,Membrane Glycoproteins ,Multidisciplinary ,Tumor Necrosis Factor-alpha ,Interleukins ,Toll-Like Receptors ,Receptors, Interleukin-1 ,Receptors, Interleukin ,Fibroblasts ,Staphylococcal Infections ,biochemical phenomena, metabolism, and nutrition ,Pedigree ,Protein Structure, Tertiary ,Phosphotransferases (Alcohol Group Acceptor) ,Interleukin-1 Receptor-Associated Kinases ,Mutation ,Codon, Terminator ,Cytokines ,Female ,Signal Transduction - 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 κB 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.
- Published
- 2003
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