Report

Pyogenic Bacterial Infections in Humans with IRAK-4 Deficiency

See allHide authors and affiliations

Science  28 Mar 2003:
Vol. 299, Issue 5615, pp. 2076-2079
DOI: 10.1126/science.1081902

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

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.

  • * To whom correspondence should be addressed. E-mail: casanova{at}necker.fr

View Full Text