Pyogenic bacterial infections in humans with IRAK-4 deficiency.
Picard C,Puel A,Bonnet M,Ku C,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 I,Frayha H,Rucker R,Hawn T,Aderem A,Tufenkeji H,Haraguchi S,Day N,Good R,Gougerot-Pocidalo M,Ozinsky A,Casanova J
Source :
2003 Mar 13
Pmid / DOI:
12637671
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.