2. Academic Validation
  3. Pyogenic bacterial infections in humans with IRAK-4 deficiency

Pyogenic bacterial infections in humans with IRAK-4 deficiency

  • Science. 2003 Mar 28;299(5615):2076-9. doi: 10.1126/science.1081902.
Capucine Picard 1,  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
Affiliations

Affiliation

  • 1 Laboratoire de Génétique Humaine des Maladies Infectieuses, Université René Descartes-INSERM U550, Faculté Necker, 156 rue de Vaugirard, 75015 Paris, France.
PMID: 12637671 DOI: 10.1126/science.1081902
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.

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